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MORI YasukoGraduate School of Medicine / Center for Infectious Diseases (CID)Professor
Researcher basic information
■ Research news- 20 Aug. 2020, Vaccine developed for human herpesvirus 6B (HHV-6B)
- 02 Sep. 2019, Professor Yasuko Mori presented with lifetime achievement award for pioneering herpes virology research
- 26 Apr. 2019, Humanization of antibodies targeting human herpesvirus 6B
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Research activity information
■ Award- Nov. 2022 兵庫県科学賞
- Jun. 2019 HHV-6 foundation, Dharam Ablashi Lifetime Achievement Award
- Oct. 2017 小島三郎記念文化賞
- Feb. 2025, iScience, 28(2) (2)Scientific journal
- A helicase-primase inhibitor, amenamevir (ASP2151), is the active pharmaceutical ingredient of a drug for the herpes zoster that is caused by reactivation of varicella-zoster virus (VZV). Here we report a new amenamevir-resistant VZV isolated under the selection pressure of amenamevir. The resistant virus has a nonsynonymous mutation K350N in the helicase gene ORF55. A recombinant virus artificially constructed harboring the ORF55 K350N also acquired amenamevir resistance, and thus the single amino-acid substitution in helicase is revealed to be responsible for the resistance. We observed that the drug-resistant virus and the ORF55 K350N recombinant virus have high resistance to amenamevir, as the EC50 values in a plaque reduction assay were > 100 μM, while the two viruses remained susceptible to the nucleoside analog drug acyclovir. No defect in viral growth was observed for these resistant viruses in a plaque size assay in human malignant melanoma cells. However, defect in plaque formation was observed from resistant virus in human fetal lung fibroblast cells, showing that the growth of the resistant virus is dependent on the cell type. We observed that the single amino-acid substitution in the helicase induces amenamevir resistance, confirming the importance of the helicase in amenamevir's inhibition of virus growth. Our findings highlight the importance of regulating the clinical use of amenamevir to minimize the risk of the emergence of helicase K350N mutation, especially in the long-term use of amenamevir by immunosuppressed patients.Nov. 2024, Journal of medical virology, 96(11) (11), e70080, English, International magazineScientific journal
- ABSTRACT The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued, enabling the virus to escape from host immunity by changing its spike antigen, while biased toward the receptor-binding domain and N-terminal domain. Here, we isolated a novel pan-SARS-CoV-2 neutralizing antibody (which we named MO11) for even the recent dominators XBB.1.16 and EG.5.1, from a convalescent patient who had received three doses of an original mRNA COVID-19 vaccination. A cryo-electron microscopy analysis of the spike-MO11 complex at 2.3 Å atomic resolution revealed that it recognizes a conserved epitope hidden behind a glycan shield at N331 on subdomain 1 (SD1), holding both the N- and C-terminal segments comprising SD1. Our identification of MO11 unveiled the functional importance of SD1 for the spike’s function, and we discuss the potential availability of a novel common epitope among the SARS-CoV-2 variants. IMPORTANCE Novel severe acute respiratory syndrome coronavirus 2 variants with immune evasion ability are still repeatedly emerging, nonetheless, a part of immunity developed in responding to the antigen of earlier variants retains efficacy against recent variants irrespective of the numerous mutations. In exploration for the broadly effective antibodies, we identified a cross-neutralizing antibody, named MO11, from the B cells of the convalescent patient. MO11 targets a novel epitope in subdomain 1 (SD1) and was effective against all emerging variants including XBB.1.16 and EG.5.1. The neutralizing activity covering from D614G to EG.5.1 variants was explained by the conservation of the epitope, and it revealed the importance of the subdomain on regulating the function of the antigen for viral infection. Demonstrated identification of the neutralizing antibody that recognizes a conserved epitope implies basal contribution of such group of antibodies for prophylaxis against COVID-19.American Society for Microbiology, Apr. 2024, Journal of VirologyScientific journal
- Nascent nucleocapsids of herpesviruses acquire a primary envelope during their nuclear export by budding through the inner nuclear membrane into the perinuclear space between the inner and outer nuclear membranes. This process is mediated by a conserved viral heterodimeric complex designated the nuclear egress complex, which consists of the nuclear matrix protein and the nuclear membrane protein. In addition to its essential roles during nuclear egress, the nuclear matrix protein has been shown to interact with intracellular signaling pathway molecules including NF-κB and IFN-β to affect viral or cellular gene expression. The human herpesvirus 6A (HHV-6A) U37 gene encodes a nuclear matrix protein, the role of which has not been analyzed. Here, we show that HHV-6A U37 activates the heat shock element promoter and induces the accumulation of the molecular chaperone Hsp90. Mechanistically, HHV-6A U37 interacts with heat shock transcription factor 1 (HSF1) and induces its phosphorylation at Ser-326. We report that pharmacological inhibition of HSF1, Hsp70, or Hsp90 decreases viral protein accumulation and viral replication. Taken together, our results lead us to propose a model in which HHV-6A U37 activates the heat shock response to support viral gene expression and replication. IMPORTANCE Human herpesvirus 6A (HHV-6A) is a dsDNA virus belonging to the Roseolovirus genus within the Betaherpesvirinae subfamily. It is frequently found in patients with neuroinflammatory disease, although its pathogenetic role, if any, awaits elucidation. The heat shock response is important for cell survival under stressful conditions that disrupt homeostasis. Our results indicate that HHV-6A U37 activates the heat shock element promoter and leads to the accumulation of heat shock proteins. Next, we show that the heat shock response is important for viral replication. Overall, our findings provide new insights into the function of HHV-6A U37 in host cell signaling and identify potential cellular targets involved in HHV-6A pathogenesis and replication.Sep. 2023, Journal of virology, 97(9) (9), e0071823, English, International magazineScientific journal
- BACKGROUND: Omicron variants with immune evasion have emerged, and they continue to mutate rapidly, raising concerns about the weakening of vaccine efficacy, and the very elderly populations are vulnerable to Coronavirus Disease 2019 (COVID-19). Therefore, to investigate the effect of multiple doses of mRNA vaccine for the newly emerged variants on these populations, cross-neutralizing antibody titers were examined against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants, including BQ.1.1 and XBB. METHODS: Blood samples were taken from residents at four long-term care facilities in Hyogo prefecture, Japan (median age, 91 years), after 3rd (n = 67) and 4th (n = 48) mRNA vaccinations, from April to October 2022. A live virus microneutralization assay was performed to determine the neutralizing antibody titers in participants' sera. RESULTS: After 3rd vaccination, cross-neutralizing antibody prevalence against conventional (D614G) virus, Delta, Omicron BA.2, BA.5, BA.2.75, BQ.1.1, and XBB were 100%, 97%, 81%, 51%, 67%, 4%, and 21%, respectively. After 4th vaccination, the antibody positivity rates increased to 100%, 100%, 98%, 79%, 92%, 31%, and 52%, respectively. The 4th vaccination significantly increased cross-neutralizing antibody titers against all tested variants. CONCLUSION: The positivity rates for BQ.1.1 and XBB increased after 4th vaccination, although the titer value was lower than those of BA.5 and BA.2.75. Considering the rapid mutation of viruses and the efficacy of vaccines, it may be necessary to create a system that can develop vaccines suitable for each epidemic in consideration of the epidemic of the virus.Jul. 2023, Journal of infection and public health, 16(7) (7), 1064 - 1072, English, International magazineScientific journal
- Abstract Immunity is known to persist after vaccination for varicella zoster virus, but the duration of immunity in patients who develop herpes zoster (HZ) remains unknown. To investigate the association between a past history of HZ and its occurrence in the general population. The Shozu HZ (SHEZ) cohort study included data for 12 299 individuals aged ≥50 years with information on their HZ history. Cross‐sectional and 3‐year follow‐up studies were carried out to analyze the associations between a history of HZ (yes <10 years, yes ≥10 years, no) and the proportion of positive varicella zoster virus skin test results (erythema diameter ≥5 mm) and the risk of HZ after adjusting for potential confounding factors including age, sex, body mass index, smoking status, sleep duration, and mental stress. The incidences of positive skin test results were 87.7% (470/536) for individuals with a history of HZ <10 years ago, 82.2% (396/482) for those with a history of HZ ≥10 years, and 80.2% (3614/4509) for those with no history of HZ. The multivariable odds ratios (95% confidence intervals) of erythema diameter ≥5 mm were 2.07 (1.57–2.73) and 1. 39 (1.08–1.80) for individuals with a history <10 years and ≥10 years ago, respectively, compared with no history. The corresponding multivariable hazard ratios of HZ were 0.54 (0.34–0.85) and 1.16 (0.83–1.61), respectively. A past history of HZ <10 years ago may reduce the occurrence of HZ.Wiley, Jun. 2023, The Journal of Dermatology, 50(9) (9), 1140 - 1144Scientific journal
- The authors aimed to identify determinants of the clinical course of herpes zoster and immunological responses, focusing on pain trajectories. This prospective community-based cohort study involved the analysis of responses to a valid pain survey provided by 375 patients diagnosed with herpes zoster based on clinical symptoms and virus identification by polymerase chain reaction. The authors analyzed most patients for humoral/cell-mediated immune response against varicella-zoster virus at the onset and 3 months post-onset. Six months post-initial visit, patients self-reported pain on a scale of 0 (no pain) to 5 (extremely strong pain) at up to 18 time points. Moreover, the pain trajectories were traced using group-based trajectory modeling. Subsequently, the authors used analysis of covariance to explore predictors and the humoral/cell-mediated immune response according to the pain trajectories. In addition, humoral/cell-mediated immune responses were assessed among each trajectory using paired t tests. Amon the five identified trajectories, two were isolated that particularly developed postherpetic neuralgia, with or without severe acute pain. Cancer therapy and corticosteroid use before herpes zoster onset specifically predicted postherpetic neuralgia without severe acute pain. In contrast, prescription of nonsteroidal anti-inflammatory drugs was uniquely associated with postherpetic neuralgia accompanied by severe acute pain. The aforementioned trajectories with postherpetic neuralgia showed increased antibodies and decreased cell-mediated immunity compared with those without postherpetic neuralgia. The authors could successfully distinguish between postherpetic neuralgia trajectories with and without severe acute pain. The identified key predictors and immunological responses against varicella-herpes zoster contribute further evidence to our understanding of the clinical features of herpes zoster and postherpetic neuralgia.May 2023, The Journal of dermatology, 50(8) (8), 1020 - 1033, English, International magazineScientific journal
- We identified neutralizing monoclonal antibodies against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) variants (including Omicron variants BA.5 and BA.2.75) from individuals who received two doses of mRNA vaccination after they had been infected with the D614G virus. We named them MO1, MO2, and MO3. Among them, MO1 showed particularly high neutralizing activity against authentic variants: D614G, Delta, BA.1, BA.1.1, BA.2, BA.2.75, and BA.5. Furthermore, MO1 suppressed BA.5 infection in hamsters. A structural analysis revealed that MO1 binds to the conserved epitope of seven variants, including Omicron variants BA.5 and BA.2.75, in the receptor-binding domain of the spike protein. MO1 targets an epitope conserved among Omicron variants BA.1, BA.2, and BA.5 in a unique binding mode. Our findings confirm that D614G-derived vaccination can induce neutralizing antibodies that recognize the epitopes conserved among the SARS-CoV-2 variants. IMPORTANCE Omicron variants of SARS-CoV-2 acquired escape ability from host immunity and authorized antibody therapeutics and thereby have been spreading worldwide. We reported that patients infected with an early SARS-CoV-2 variant, D614G, and who received subsequent two-dose mRNA vaccination have high neutralizing antibody titer against Omicron lineages. It was speculated that the patients have neutralizing antibodies broadly effective against SARS-CoV-2 variants by targeting common epitopes. Here, we explored human monoclonal antibodies from B cells of the patients. One of the monoclonal antibodies, named MO1, showed high potency against broad SARS-CoV-2 variants including BA.2.75 and BA.5 variants. The results prove that monoclonal antibodies that have common neutralizing epitopes among several Omicrons were produced in patients infected with D614G and who received mRNA vaccination.May 2023, Journal of virology, e0028623, English, International magazineScientific journal
- Genotype IV Japanese encephalitis (JE) virus (GIV JEV) is the least common and most neglected genotype in JEV. We evaluated the growth and pathogenic potential of the GIV strain 19CxBa-83-Cv, which was isolated from a mosquito pool in Bali, Indonesia, in 2019, and serological analyses were also conducted. The growth ability of 19CxBa-83-Cv in Vero cells was intermediate between that of the genotype I (GI) strain Mie/41/2002 and the genotype V (GV) strain Muar, whereas 19CxBa-83-Cv and Mie/41/2002 grew faster than Muar in mouse neuroblastoma cells. The neuroinvasiveness of 19CxBa-83-Cv in mice was higher than that of Mie/41/2002 but lower than that of Muar; however, there were no significant differences in neurovirulence in mice among the three strains. The neutralizing titers of sera from 19CxBa-83-Cv- and Mie/41/2002-inoculated mice against 19CxBa-83-Cv and Mie/41/2002 were similar, whereas the titers against Muar were lower than those of the other two viruses. The neutralizing titers of JE vaccine-inoculated mouse pool serum against 19CxBa-83-Cv and Muar were significantly lower than those against Mie/41/2002. The neutralizing titers against the three viruses were similar in three out of the five serum samples from GI-infected JE patients, although the titers against Mie/41/2002 were higher than those against 19CxBa-83-Cv and Muar in the remaining two sera samples. In summary, we identified the basic characteristics of 19CxBa-83-Cv, but further studies are needed to better understand GIV JEV.Jan. 2023, Viruses, 15(1) (1), English, International magazineScientific journal
- BACKGROUND: Varicella-zoster virus-specific cell-mediated immunity has been associated with the onset and severity of herpes zoster (HZ), and the administration of the HZ vaccine enhanced the immunity. However, limited data is available on the duration of cell-mediated immunity enhancement by soluble antigen of varicella-zoster virus (VZV) skin test. METHODS: A prospective, community-based cohort study was conducted in Shozu County, Kagawa Prefecture, Japan. Repeated VZV skin tests containing inactivated VZV antigen and blood tests were performed on 365 subjects aged 60 years and older at baseline, 1, 2, and 3 years later. The differential immunity indices of VZV over time for cell-mediated and humoral immunity were evaluated. RESULTS: VZV skin test reaction and ELISpot counts increased significantly at 1, 2, and 3 years later compared to the baseline. However, humoral immunity indices did not change materially over time. CONCLUSION: Soluble antigen by VZV skin test enhanced VZV-specific cell-mediated immunity, and it persisted for at least one year. In addition, the inoculation with inactivated antigens every year by VZV skin test continued to enhance VZV-specific cell-mediated immunity after 2 and 3 years. This article is protected by copyright. All rights reserved.Nov. 2022, Journal of medical virology, 95(1) (1), e28336, English, International magazineScientific journal
- The stimulus-induced cAMP response element (CRE)-binding protein (CREB) family of transcription factors bind to CREs to regulate diverse cellular responses, including proliferation, survival, and differentiation. Human herpesvirus 6A (HHV-6A), which belongs to the Betaherpesvirinae subfamily, is a lymphotropic herpesvirus frequently found in patients with neuroinflammatory diseases. Previous reports implicated the importance of CREs in the HHV-6A life cycle, although the effects of the binding of transcription factors to CREs in viral replication have not been fully elucidated. In this study, we analyzed the role of the CREB family of transcription factors during HHV-6A replication. We found that HHV-6A infection enhanced phosphorylation of the CREB family members CREB1 and activating transcription factor 1 (ATF1). Knockout (KO) of CREB1 or ATF1 enhanced viral gene expression and viral replication. The increase in viral yields in supernatants from ATF1-KO cells was greater than that in supernatants from CREB1-KO cells. Transcriptome sequencing (RNA-seq) analysis showed that sensors of the innate immune system were downregulated in ATF1-KO cells, and mRNAs of beta interferon (IFN-β) and IFN-regulated genes were reduced in these cells infected with HHV-6A. IFN-β treatment of ATF1-KO cells reduced progeny viral yields significantly, suggesting that the enhancement of viral replication was caused by a reduction of IFN-β. Taken together, our results suggest that ATF1 is activated during HHV-6A infection and restricts viral replication via IFN-β induction. IMPORTANCE Human herpesvirus 6A (HHV-6A) is a ubiquitous herpesvirus implicated in Alzheimer's disease, although its role in its pathogenesis has not been confirmed. Here, we showed that the transcription factor ATF1 restricts HHV-6A replication, mediated by IFN-β induction. Our study provides new insights into the role of ATF1 in innate viral immunity and reveals the importance of IFN-β for regulation of HHV-6A replication, which possibly impairs HHV-6A pathogenesis.Oct. 2022, Journal of virology, 96(19) (19), e0126422, English, International magazineScientific journal
- Sep. 2022, The Journal of infectious diseases, 226(11) (11), 2041 - 2042, English, International magazineScientific journal
- Summary We identified novel neutralizing monoclonal antibodies against SARS-CoV-2 variants (including Omicron) from individuals received two doses of mRNA vaccination after they had been infected with wildtype. We named them MO1, MO2 and MO3. MO1 shows high neutralizing activity against authentic variants: D614G, Delta, BA.1, BA.1.1, BA.2, and BA.2.75 and BA.5. Our findings confirm that the wildtype-derived vaccination can induce neutralizing antibodies that recognize the epitopes conserved among the SARS-CoV-2 variants (including BA.5 and BA.2.75). The monoclonal antibodies obtained herein could serve as novel prophylaxis and therapeutics against not only current SARS-CoV-2 viruses but also future variants that may arise.Cold Spring Harbor Laboratory, Sep. 2022
- Anti-CD20 antibodies react with CD20 expressed not only on malignant B cells, but also on normal B cells. It has been reported that patients treated with anti-CD20 antibodies had an insufficient response to two-dose mRNA SARS-CoV-2 vaccination. To investigate the efficacy of a third dose in these patients, we investigated serum IgG antibody titers for the S1 protein after a third vaccination in 22 patients treated with the anti-CD20 antibody who failed two-dose vaccination. Results showed that overall, 50% of patients seroconverted. Although no patient who received the third dose within 1 year of the last anti-CD20 antibody administration showed an increase in S1 antibody titer, 69% of patients who received the third dose more than 1 year after the last anti-CD20 antibody administration seroconverted. Our data show that a third dose of vaccination is effective in improving the seroconversion rate in patients treated with the anti-CD20 antibody who failed standard two-dose vaccination.Jun. 2022, Vaccines, 10(6) (6), English, International magazineScientific journal
- The SARS-CoV-2 variant Omicron is now under investigation. We evaluated cross-neutralizing activity against Omicron in COVID-19 convalescent patients (n = 23) who had received two doses of an mRNA vaccination (BNT162b2 or mRNA-1273). Intriguingly, after the second vaccination, the neutralizing antibody titers of subjects against SARS-CoV-2 variants, including Omicron, all became seropositive, and significant fold-increases (21.1-52.0) were seen regardless of the disease severity of subjects. Our findings thus demonstrate that two doses of mRNA vaccination to SARS-CoV-2 convalescent patients can induce cross-neutralizing activity against Omicron.May 2022, The Journal of infectious diseases, English, International magazineScientific journal
- Importance: Although 2 and 3 doses of vaccine have been implemented against the SARS-CoV-2 pandemic, the level of immunity achieved by these additional vaccinations remains unclear. Objective: To investigate the induction of neutralizing antibodies against the SARS-CoV-2 Omicron variant after 2 and 3 doses of the BNT162b2 messenger RNA (mRNA) vaccine among recipients of different ages. Design, Setting, and Participants: A cohort study was conducted from June 1, 2021, to January 12, 2022, among 82 physicians at Kobe University Hospital who had received 2 doses of the BNT162b2 mRNA vaccine. Main Outcomes and Measures: The rates of positive test results and the titers of neutralizing antibodies against the Omicron variant after 2 and 3 doses of the vaccine were compared with those against other variants and compared among 3 age groups (≤38 years [younger age group], 39-58 years [intermediate age group], and ≥59 years [older age group]). Results: A total of 82 physicians (71 men [87%]; median age, 44 years [IQR, 33-58 years]) participated; 31 (38%) were in the younger age group, 32 (39%) were in the intermediate age group, and 19 (23%) were in the older age group. At 2 months after 2 doses of the vaccine, 23 participants (28%) had neutralizing antibodies against the Omicron variant, with a titer of 1.3 (95% CI, 1.2-1.4), which was 11.8-fold (95% CI, 9.9-13.9) lower than the titer against the D614G variant and the lowest among the variants tested. Although the titer of the neutralizing antibody against the Delta variant tended to be low among the older age group (2.9 [95% CI, 2.0-4.1]), the titers of the neutralizing antibody against the Omicron variant were low among all age groups (younger age group, 1.3 [95% CI, 1.1-1.6]; intermediate age group, 1.3 (95% CI, [95% CI, 1.1-1.5]; and older age group, 1.2 [95% CI, 1.0-1.4]). At 7 months after 2 doses of the vaccine, 5 participants (6%) had the neutralizing antibody against the Omicron variant, but after the booster (third dose) vaccination, all 72 participants who received the booster had the neutralizing antibody, and the titer was 41 (95% CI, 34-49), much higher than that at 7 months after 2 doses of the vaccine (1.0 [95% CI, 1.0-1.1]). This increase in titers was observed regardless of age groups; the titers were 44 (95% CI, 32-59) among the younger age group, 44 (95% CI, 32-59) among the intermediate age group, and 30 (95% CI, 22-41) among the older age group. Conclusions and Relevance: In this cohort study of 82 Japanese participants, 2 doses of the BNT162b2 mRNA vaccine did not induce sufficient neutralizing antibody against the Omicron variant. However, booster vaccination was associated with induction of a high level of neutralizing antibodies against the Omicron variant, irrespective of the recipient's age.May 2022, JAMA network open, 5(5) (5), e2210780, English, International magazineScientific journal
- Apr. 2022, The Journal of infectious diseases, English, International magazineScientific journal
- BACKGROUND: Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe adverse drug reaction commonly associated with the reactivation of human herpesvirus 6 (HHV-6). There are currently no adequate biomarkers for the early diagnosis and detection of DIHS/DRESS. Notably, OX40 (CD134) has an important role in allergic inflammation and functions as a cellular receptor for HHV-6 entry. We previously reported that the membrane-bound form of OX40 in CD4+ T cells was upregulated in DIHS/DRESS. OBJECTIVE: We sought to investigate the clinical significance of serum soluble OX40 (sOX40) in DIHS/DRESS. METHODS: Serum sOX40 levels in patients with DIHS/DRESS (n = 39), maculopapular exanthema/erythema multiforme (n = 17), Stevens-Johnson syndrome/toxic epidermal necrolysis (n = 13), or autoimmune bullous diseases (n = 5), and levels in healthy volunteers (n = 5) were examined by enzyme-linked immunosorbent assay. Copy numbers of HHV-6, HHV-7, and cytomegalovirus in peripheral blood mononuclear cells were quantified using real-time PCR. RESULTS: Serum sOX40 levels in patients with DIHS/DRESS in the acute stage were elevated in parallel with high OX40 expression on CD4+ T cells. Serum sOX40 levels were significantly positively correlated with disease severity and serum levels of thymus and activation-regulated chemokine, IL-5, and IL-10. Human herpesvirus 6-positive patients had higher sOX40 levels than did HHV-6-negative patients, and serum sOX40 levels were correlated with HHV-6 DNA loads. CONCLUSIONS: Serum sOX40 levels can be a useful diagnostic marker for DIHS/DRESS that reflect disease severity. Elevated serum sOX40 levels also predict HHV-6 reactivation in patients with DIHS/DRESS.Feb. 2022, The journal of allergy and clinical immunology. In practice, 10(2) (2), 558 - 565, English, International magazineScientific journal
- BACKGROUND: We investigated whether family histories of herpes zoster (HZ) are associated with the risk of incident HZ in a Japanese population. METHODS: A total of 12,522 Japanese residents aged ≥50 years in Shozu County participated in the baseline survey between December 2008 and November 2009 (the participation rate = 72.3%). They were interviewed at baseline by research physicians regarding the registrants' history of HZ. A self-administered questionnaire survey was conducted to evaluate the potential confounding factors. 10,530 participants without a history of HZ were followed up to ascertain the incidence of HZ during 3-years follow-up until the end of November 2012 with Japanese nationals. We estimated hazard ratios (HRs) of incident HZ according to first-degree family histories using the Cox proportional hazard regression after adjusting for age, sex, and other potential confounding factors. RESULTS: Compared to no HZ history of each family member, a history of brother or sister was associated with a higher risk of incident HZ while histories of father and mother were not. The multivariable HR (95%CI) of incident HZ for a history of brother or sister was 1.67 (1.04-2.69). When comparing to no family histories of all first-degree relatives, the multivariable HRs (95%CIs) were 1.34 (0.77-2.34) for a history of brother or sister alone, but 4.81 (1.78-13.00) for a history of mother plus brother or sister. As for the number of family histories, the multivariable HRs (95%CIs) were 1.08 (0.76-1.54) for one relative (father, mother, or brother or sister) and 2.75 (1.13-6.70) for two or more relatives. CONCLUSION: Family histories of mother plus brother or sister and two or more first-degree relatives were associated with a higher risk of incident HZ.2022, Environmental health and preventive medicine, 27, 22 - 22, English, Domestic magazineScientific journal
- Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus responsible for the Coronavirus Disease 2019 (COVID-19) pandemic. The emergence of variants of concern (VOCs) has become one of the most pressing issues in public health. To control VOCs, it is important to know which COVID-19 convalescent sera have cross-neutralizing activity against VOCs and how long the sera maintain this protective activity. Methods: Sera of patients infected with SARS-CoV-2 from March 2020 to January 2021 and admitted to Hyogo Prefectural Kakogawa Medical Center were selected. Blood was drawn from patients at 1-3, 3-6, and 6-8 months post onset. Then, a virus neutralization assay against SARS-CoV-2 variants (D614G mutation as conventional strain; B.1.1.7, P.1, and B.1.351 as VOCs) was performed using authentic viruses. Results: We assessed 97 sera from 42 patients. Sera from 28 patients showed neutralizing activity that was sustained for 3-8 months post onset. The neutralizing antibody titer against D614G significantly decreased in sera of 6-8 months post onset compared to those of 1-3 months post onset. However, the neutralizing antibody titers against the three VOCs were not significantly different among 1-3, 3-6, and 6-8 months post onset. Discussion: Our results indicate that neutralizing antibodies that recognize the common epitope for several variants may be maintained for a long time, while neutralizing antibodies having specific epitopes for a variant, produced in large quantities immediately after infection, may decrease quite rapidly.2022, Frontiers in immunology, 13, 773652 - 773652, English, International magazineScientific journal
- Continuous appearance of SARS-CoV-2 variants and mass vaccination have been intricately influencing on the COVID-19 situation. To elucidate the current status in Japan, we analyzed totally 2,000 sera in August (n = 1,000) and December (n = 1,000) 2021 collected from individuals who underwent a health check-up. The anti-N seropositive rate were 2.1% and 3.9% in August and December 2021, respectively, demonstrating a Delta variant endemic during that time; it was approximately twofold higher than the rate based on the PCR-based diagnosis. The anti-S seropositive rate was 38.7% in August and it reached 90.8% in December, in concordance with the vaccination rate in Japan. In the December cohort, 78.7% of the sera showed neutralizing activity against the Delta variant, whereas that against the Omicron was much lower at 36.6%. These analyses revealed that effective immunity against the Delta variant was established in December 2021, however, prompt three-dose vaccination is needed to overcome Omicron's outbreak.2022, PloS one, 17(4) (4), e0266270, English, International magazineScientific journal
- We investigated the efficacy of BNT162b2 mRNA COVID-19 vaccine in patients with B-cell malignancies treated with anti-CD20 antibody. Although T-cell-mediated immune responses were detected even in patients receiving R-CHOP treatment, the S1 antibody titer following BNT162b2 vaccination remained only marginally increased for more than 3 years after the final dose of anti-CD20 antibody. We found no relationship between the percent of B-cells and S1 antibody titer. The duration of this suppression was much longer than we anticipated. Further protection and treatment strategies against COVID-19 for these patients are warranted.Jan. 2022, International journal of hematology, 115(1) (1), 7 - 10, English, Domestic magazineScientific journal
- BACKGROUND: Although COVID-19 severity in cancer patients is high, the safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients undergoing chemotherapy for solid cancers in Japan have not been reported. METHODS: We investigated the safety and immunogenicity of BNT162b2 in 41 patients undergoing chemotherapy for solid cancers and in healthy volunteers who received 2 doses of BNT162b2. We evaluated serum IgG antibody titers for S1 protein by ELISA at pre-vaccination, prior to the second dose and 14 days after the second vaccination in 24 cancer patients undergoing cytotoxic chemotherapy (CC group), 17 cancer patients undergoing immune checkpoint inhibitor therapy (ICI group) and 12 age-matched healthy volunteers (HV group). Additionally, inflammatory cytokine levels were compared between the HV and ICI groups at pre and the next day of each vaccination. RESULTS: Anti-S1 antibody levels were significantly lower in the ICI and CC groups than in the HV group after the second dose (median optimal density: 0.241 [0.063-1.205] and 0.161 [0.07-0.857] vs 0.644 [0.259-1.498], p = 0.0024 and p < 0.0001, respectively). Adverse effect profile did not differ among the three groups, and no serious adverse event occurred. There were no differences in vaccine-induced inflammatory cytokines between the HV and ICI groups. CONCLUSION: Although there were no significant differences in adverse events in three groups, antibody titers were significantly lower in the ICI and CC groups than in the HV group. Further protection strategies should be considered in cancer patients undergoing CC or ICI.Dec. 2021, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 28(4) (4), 516 - 520, English, International magazineScientific journal
- During the nuclear export of nascent nucleocapsids of herpesviruses, the nucleocapsids bud through the inner nuclear membrane (INM) by acquiring the INM as a primary envelope (primary envelopment). We recently reported that herpes simplex virus 1 (HSV-1) nuclear egress complex (NEC), which consists of UL34 and UL31, interacts with an ESCRT-III adaptor ALIX and recruits ESCRT-III machinery to the INM for efficient primary envelopment. In this study, we identified a cluster of six arginine residues in the disordered domain of UL34 as a minimal region required for the interaction with ALIX as well as the recruitment of ALIX and an ESCRT-III protein CHMP4B to the INM in HSV-1-infected cells. Mutations in the arginine cluster exhibited phenotypes similar to those with ESCRT-III inhibition reported previously, including the mis-localization of NEC, induction of membranous invagination structures containing enveloped virions, aberrant accumulation of enveloped virions in the invaginations and perinuclear space, and reduction of viral replication. We also showed that the effect of the arginine cluster in UL34 on HSV-1 replication was dependent primarily on ALIX. These results indicated that the arginine cluster in the disordered domain of UL34 was required for the interaction with ALIX and the recruitment of ESCRT-III machinery to the INM to promote primary envelopment. IMPORTANCE Herpesvirus UL34 homologs contain conserved amino-terminal domains that mediate vesicle formation through interactions with UL31 homologs during primary envelopment. UL34 homologs also comprise other domains adjacent to their membrane-anchoring regions, which differ in length, are variable in herpesviruses and do not form distinguished secondary structures. However, the role of these disordered domains in infected cells remains to be elucidated. In this study, we present data suggesting that the arginine cluster in the disordered domain of HSV-1 UL34 mediates the interaction with ALIX, thereby leading to the recruitment of ESCRT-III machinery to the INM for efficient primary envelopment. This is the first study to report the role of the disordered domain of a UL34 homolog in herpesvirus infections.Nov. 2021, Journal of virology, JVI0170421, English, International magazineScientific journal
- Serum Cytokine Profiles of Rapid Recovery Patients with COVID-19: Series of 6 Cases.COVID-19 patients reveal various clinical manifestations; however, the specific mechanisms and factors contributing to rapid recovery remain unclear. We performed serum cytokine profiling using a bead-based immunoassay in six COVID-19 patients with mild symptoms who experienced rapid recovery. All patients had fever that resolved within 4 days. During the study, the interferon gamma-related protein 10 (IP-10) level rapidly increased initially, and then rapidly decreased in all six patients. Similarly, the interferon (IFN)-λ 2/3 levels rapidly increased initially, and then decreased in five of the six patients. IP-10 and IFN-λ2/3 may play a key role in the rapid recovery of mild COVID-19.Oct. 2021, The Kobe journal of medical sciences, 67(2) (2), E55-E60, English, Domestic magazineScientific journal
- Background: As of March 2021, Japan is facing a fourth wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To prevent further spread of infection, sera cross-neutralizing activity of patients previously infected with conventional SARS-CoV-2 against novel variants is important but has not been firmly established. Methods: We investigated the neutralizing potency of 81 coronavirus disease 2019 (COVID-19) patients' sera from the first to fourth waves of the pandemic against SARS-CoV-2 D614G, B.1.1.7, P.1, and B.1.351 variants using their authentic viruses. Results: Most sera had neutralizing activity against all variants, showing similar activity against B.1.1.7 and D614G, but lower activity especially against B.1.351. In the fourth wave, sera-neutralizing activity against B.1.1.7 was significantly higher than that against any other variants, including D614G. The sera-neutralizing activity in less severe patients was lower than that of more severe patients for all variants. Conclusions: The cross-neutralizing activity of convalescent sera was effective against all variants but was potentially weaker for B.1.351. The high neutralizing activity specific to B.1.1.7 in the fourth wave suggests that mutations in the virus might cause conformational change of its spike protein, which affects immune recognition of D614G. Our results indicate that individuals who recover from COVID-19 could be protected from the severity caused by infection with newly emerging variants.Corresponding, Oct. 2021, Open forum infectious diseases, 8(10) (10), ofab430, English, International magazine[Refereed]Scientific journal
- Cold Spring Harbor Laboratory, Sep. 2021
Abstract The situation of the COVID-19 pandemic in Japan is drastically changing in the 2nd year, 2021, due to the appearance of SARS-CoV-2 variants of concern and the roll-out of mass vaccination. In addition to PCR diagnosis, periodic seroepidemiologic surveillance is important to analyze the epidemic situation. In this study, we analyzed the rate of seropositivity for the SARS-CoV-2 N and S antigens in Hyogo prefecture, Japan in August 2021. Sera collected from people who received a health check-up in a clinic of the Hyogo Prefecture Health Promotion Association were subjected to analysis of reactivity to the SARS-CoV-2 N and S antigens by electrochemiluminescence immunoassay (ECLIA) and enzyme-linked immunosorbent assay (ELISA), respectively. For a total 1,000 sera, the positive rates to N and S antigens were 2.1% and 38.7%, respectively. The infectious rate estimated by serological analysis based on the presence of the anti-N antibody was 2.5-fold higher than the value reported based on PCR-based analysis, and it increased five-fold compared to the rate determined by our previous seroepidemiologic study in October, 2020. The anti-S positive rate was almost consistent with the vaccination rate in this area. The observed high anti-S antibody level in the seropositive population may indicate that the mass vaccination in Japan is being performed smoothly at this time point, although the infectious rate has also increased. - Viral infection induces host cells to mount a variety of immune responses, which may either limit viral propagation or create conditions conducive to virus replication in some instances. In this regard, activation of the NF-κB transcription factor is known to modulate virus replication. Human herpesvirus 6A (HHV-6A), which belongs to the Betaherpesvirinae subfamily, is frequently found in patients with neuro-inflammatory diseases, although its role in disease pathogenesis has not been elucidated. In this study, we found that the HHV-6A-encoded U14 protein activates NF-κB signaling following interaction with the NF-κB complex protein, p65. Through induction of nuclear translocation of p65, U14 increases the expression of IL-6, IL-8 and MCP-1 transcripts. We also demonstrated that activation of NF-κB signaling is important for HHV-6A replication, as inhibition of this pathway reduced virus protein accumulation and viral genome copy number. Taken together, our results suggest that HHV-6A infection activates the NF-κB pathway and promotes viral gene expression via late gene products including U14. IMPORTANCE Human herpesvirus 6A (HHV-6A) is frequently found in patients with neuro-inflammation, although its role in the pathogenesis of this disease has not been elucidated. Most viral infections activate the NF-κB pathway, which causes the transactivation of various genes, including those encoding pro-inflammatory cytokines. Our results indicate that HHV-6A U14 activates the NF-κB pathway, leading to upregulation of pro-inflammatory cytokines. We also found that activation of the NF-κB transcription factor is important for efficient viral replication. This study provides new insight into HHV-6A U14 function in host cell signaling, and identifies potential cellular targets involved in HHV-6A pathogenesis and replication.Sep. 2021, Journal of virology, JVI0126921, English, International magazine[Refereed]Scientific journal
- Background: Antibody production is one of the primary mechanisms for recovery from coronavirus disease 2019 (COVID-19). It is speculated that massive clonal expansion of B cells, which can produce clinically meaningful neutralizing antibodies, occurs in patients who recover on the timing of acquiring adaptive immunity. Methods: To evaluate fluctuations in clonal B cells and the size of the clones, we chronologically assessed the B-cell receptor (BCR) repertoire in three patients with COVID-19 who recovered around 10 days after symptom onset. Results: We focused on the three dominant clonotypes (top 3) in each individual. The percentage frequencies of the top 3 clonotypes increased rapidly and accounted for 27.8 % on day 9 in patient 1, 10.4 % on day 12 in patient 2, and 10.8 % on day 11 in patient 3, respectively. The frequencies of these top 3 clonotypes rapidly decreased as the patients' clinical symptoms improved. Furthermore, BCR network analysis revealed that accumulation of clusters composed of similar complementarity-determining region 3 (CDR3) sequences were rapidly formed, grew, and reached their maximum size around 10 days after symptom onset. Conclusions: BCR repertoire analysis revealed that a massive surge of some unique BCRs occurs during the acquisition of adaptive immunity and recovery. The peaks were more prominent than expected. These results provide insight into the important role of BCRs in the recovery from COVID-19 and raise the possibility of developing neutralizing antibodies as COVID-19 immunotherapy.Aug. 2021, Heliyon, 7(8) (8), e07748, English, International magazine[Refereed]Scientific journal
- Japanese encephalitis virus (JEV) is transmitted between swine, migratory birds, and Culex mosquitoes, and has circulated indigenously in Asia for almost a century. Despite being the country with the highest JEV diversity, surveillance targeting of Indonesia's vectors is scarce. This study collected mosquitoes from several locations in Tabanan Regency, Bali Island, Indonesia. We captured and classified 3,032 adult Culex mosquitoes into seven species, with Culex vishnui subgroup mosquitoes making up approximately 90% of the total. Japanese encephalitis virus was identified by next-generation sequencing (NGS) analysis of a Cx. vishnui mosquito pool. Genetic and phylogenetic analysis revealed the JEV as genotype (G) IV. The nucleotide identity was 99% with other JEV GIV isolates obtained from swine sera in 2017 on Bali Island and from a human patient in Australia with a travel history to Bali in 2019. This finding indicated that JEV GIV persists in restricted areas and is circulating between swine-mosquito vectors.Jul. 2021, The American journal of tropical medicine and hygiene, 105(3) (3), 813 - 817, English, International magazine[Refereed]Scientific journal
- Like all herpesviruses, the roseoloviruses (HHV6A, -6B, and -7) establish lifelong infection within their host, requiring these viruses to evade host antiviral responses. One common host-evasion strategy is the downregulation of host-encoded, surface-expressed glycoproteins. Roseoloviruses have been shown to evade the host immune response by downregulating NK-activating ligands, class I MHC, and the TCR/CD3 complex. To more globally identify glycoproteins that are differentially expressed on the surface of HHV6A-infected cells, we performed cell surface capture of N-linked glycoproteins present on the surface of T cells infected with HHV6A, and compared these to proteins present on the surface of uninfected T cells. We found that the protein tyrosine phosphatase CD45 is downregulated in T cells infected with HHV6A. We also demonstrated that CD45 is similarly downregulated in cells infected with HHV7. CD45 is essential for signaling through the T cell receptor and, as such, is necessary for developing a fully functional immune response. Interestingly, the closely related betaherpesviruses human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV) have also separately evolved unique mechanisms to target CD45. While HCMV and MCMV target CD45 signaling and trafficking, HHV6A acts to downregulate CD45 transcripts. IMPORTANCE Human herpesviruses-6 and -7 infect essentially 100% of the world's population before the age of 5 and then remain latent or persistent in their host throughout life. As such, these viruses are among the most pervasive and stealthy of all viruses. Host immune cells rely on the presence of surface-expressed proteins to identify and target virus-infected cells. Here, we investigated the changes that occur to proteins expressed on the cell surface of T cells after infection with human herpesvirus-6A. We discovered that HHV-6A infection results in a reduction of CD45 on the surface of infected T cells and impaired activation in response to T cell receptor stimulation.Jun. 2021, Journal of virology, 95(14) (14), e0162820, English, International magazine[Refereed]Scientific journal
- BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global health problem that causes millions of deaths worldwide. The clinical manifestation of COVID-19 widely varies from asymptomatic infection to severe pneumonia and systemic inflammatory disease. It is thought that host genetic variability may affect the host's response to the virus infection and thus cause severity of the disease. The SARS-CoV-2 virus requires interaction with its receptor complex in the host cells before infection. The transmembrane protease serine 2 (TMPRSS2) has been identified as one of the key molecules involved in SARS-CoV-2 virus receptor binding and cell invasion. Therefore, in this study, we investigated the correlation between a genetic variant within the human TMPRSS2 gene and COVID-19 severity and viral load. RESULTS: We genotyped 95 patients with COVID-19 hospitalised in Dr Soetomo General Hospital and Indrapura Field Hospital (Surabaya, Indonesia) for the TMPRSS2 p.Val160Met polymorphism. Polymorphism was detected using a TaqMan assay. We then analysed the association between the presence of the genetic variant and disease severity and viral load. We did not observe any correlation between the presence of TMPRSS2 genetic variant and the severity of the disease. However, we identified a significant association between the p.Val160Met polymorphism and the SARS-CoV-2 viral load, as estimated by the Ct value of the diagnostic nucleic acid amplification test. Furthermore, we observed a trend of association between the presence of the C allele and the mortality rate in patients with severe COVID-19. CONCLUSION: Our data indicate a possible association between TMPRSS2 p.Val160Met polymorphism and SARS-CoV-2 infectivity and the outcome of COVID-19.May 2021, Human genomics, 15(1) (1), 29 - 29, English, International magazine[Refereed]Scientific journal
- BACKGROUND: The impact of body mass index on incidence of herpes zoster is unclear. This study investigated whether it was associated with a history of herpes zoster and incidence during a 3-year follow-up, using data from a prospective cohort study in Japan. METHODS: In total, 12,311 individuals were included in the cross-sectional analysis at baseline, of whom 1,818 with a history of herpes zoster were excluded from the incidence analysis, leaving 10,493 individuals. Body mass index (kg/m2) was classified into three categories (underweight < 18.5, normal 18.5 to < 25, and overweight ≥ 25). To evaluate the risk of herpes zoster, we used a logistic regression model for prevalence, and a Cox proportional hazard regression model for incidence. RESULTS: Being overweight or underweight was not associated with herpes zoster prevalence at baseline. The multivariate hazard ratios (95% confidence intervals) of herpes zoster incidence for overweight versus normal-weight groups were 0.67 (0.51-0.90) in all participants, and 0.57 (0.39-0.83) in women, with no significant difference for men. CONCLUSIONS: Being overweight was associated with a lower incidence of herpes zoster than being normal weight in older Japanese women.Feb. 2021, Journal of epidemiology, 32(8) (8), 370 - 375, English, Domestic magazine[Refereed]Scientific journal
- Patients with coronavirus disease 2019 (COVID-19) exhibit a wide clinical spectrum ranging from mild respiratory symptoms to critical and fatal diseases, and older individuals are known to be more severely affected. The underlying mechanism of this phenomenon is unknown. A neutralizing antibody against viruses is known to be important to eliminate the virus. In addition, this antibody is induced at high levels in patients with severe COVID-19, followed by a termination of virus replication. Severe COVID-19 patients exhibit high levels of cytokines/chemokines, even after the disappearance of the virus. This indicates that cytokines/chemokines play significant roles in disease severity. These findings also suggest that antiviral therapy (monoclonal antibody and/or convalescent plasma therapy) should be administered early to eliminate the virus, followed by steroid treatment after viral genome disappearance, especially in patients with severe symptoms.Corresponding, Jan. 2021, JMA journal, 4(1) (1), 1 - 7, English, International magazine[Refereed]Scientific journal
- Introduction: The coronavirus disease 2019 (COVID-19) pandemic is spreading rapidly all over the world. The Japanese government lifted the state of emergency, announced in April 2020, on May 25, but there are still sporadic clusters. Asymptomatic patients who can transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause some of these clusters. It is thus urgent to investigate the seroprevalence of antibodies against SARS-CoV-2 and their neutralizing activity. We conducted a cross-sectional study of >10,000 samples at hospitals in Hyogo Prefecture, Japan. Methods: Between August 6 and October 1, 2020, we collected samples of residual blood from the patients who visited or were admitted to five hospitals and a foundation in Hyogo. We tested the samples for antibodies against SARS-CoV-2 by electrochemiluminescence immunoassay (ECLIA) and chemiluminescent enzyme immunoassay (CLEIA). Sera that were positive by ECLIA or CLEIA were analyzed by an immunochromatographic (IC) test and neutralizing activity assay. Results: We tested 10,377 samples from patients aged between 0 and 99 years old; 27 cases (0.26%) were positive on the ECLIA, and 51 cases (0.49%) were positive on CLEIA. In the 14 cases that tested positive on both ECLIA and CLEIA, the positive rates on the IC test and for neutralizing activity were high (85% and 92%, respectively). In 50 cases (0.48%) that were positive by either ECLIA or CLEIA, the corresponding rates were low (20% and 6%, respectively). The positive rate of neutralizing antibody was 0.15%. Conclusions: These results indicate that most Hyogo Prefecture residents still do not have antibodies and should avoid the risk of incurring a SARS-CoV-2 infection. Two or more antibody tests should be required for seroepidemiological studies of the antibody for SARS-CoV-2, and a neutralizing activity assay is also essential.Corresponding, Jan. 2021, JMA journal, 4(1) (1), 41 - 49, English, International magazine[Refereed]Scientific journal
- Viral cell-to-cell spread, a method employed by several viral families for entrance via cell junctions, is highly relevant to the pathogenesis of various viral infections. Cell-to-cell spread of herpes simplex virus 1 (HSV-1) is known to depend greatly on envelope glycoprotein E (gE). However, the molecular mechanism by which gE acts in HSV-1 cell-to-cell spread and the mechanisms of cell-to-cell spread by other herpesviruses remain poorly understood. Here, we describe our identification of prohibitin-1 as a novel gE-interacting host cell protein. Ectopic expression of prohibitin-1 increased gE-dependent HSV-1 cell-to-cell spread. As observed with the gE-null mutation, decreased expression or pharmacological inhibition of prohibitin-1 reduced HSV-1 cell-to-cell spread without affecting the yield of virus progeny. Similar effects were produced by pharmacological inhibition of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway, wherein prohibitin-1 acts as a protein scaffold and is required for induction of this pathway. Furthermore, artificial activation of the MAPK/ERK pathway restored HSV-1 cell-to-cell spread impaired by the gE-null mutation. Notably, pharmacological inhibition of prohibitins or the MAPK/ERK pathway reduced viral cell-to-cell spread of representative members in all herpesvirus subfamilies. Our results suggest that prohibitin-1 contributes to gE-dependent HSV-1 cell-to-cell spread via the MAPK/ERK pathway and that this mechanism is conserved throughout the Herpesviridae, whereas gE is conserved only in the Alphaherpesvirinae subfamily.IMPORTANCE Herpesviruses are ubiquitous pathogens of various animals, including humans. These viruses primarily pass through cell junctions to spread to uninfected cells. This method of cell-to-cell spread is an important pathogenic characteristic of these viruses. Here, we show that the host cell protein prohibitin-1 contributes to HSV-1 cell-to-cell spread via a downstream intracellular signaling cascade, the MAPK/ERK pathway. We also demonstrate that the role of the prohibitin-1-mediated MAPK/ERK pathway in viral cell-to-cell spread is conserved in representative members of every herpesvirus subfamily. This study has revealed a common molecular mechanism of the cell-to-cell spread of herpesviruses.Jan. 2021, Journal of virology, 95(3) (3), English, International magazine[Refereed]Scientific journal
- Most COVID-19 patients experience asymptomatic/mild symptoms, but some suffer critical symptoms requiring intensive care. It is important to determine how asymptomatic/mild patients react to SARS-CoV-2 infection and suppress virus spread. Innate immunity is important for evasion from the first virus attack, and it may play an important role in the pathogenesis in these patients. We measured serum cytokine levels of 95 COVID-19 patients during the infection's acute phase and are first to report that significantly higher IL-12 and IL-2 levels were induced in asymptomatic/mild patients versus those in the moderate/severe patients, indicating these cytokines' key roles in asymptomatic/mild infections' pathogenesis.Corresponding, Jan. 2021, The Journal of infectious diseases, 223(7) (7), 1145 - 1149, English, International magazine[Refereed]Scientific journal
- Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a global pandemic, including Indonesia. However, there are only limited data regarding the precise prevalence of the COVID-19 pandemic in Indonesia. Here, to estimate the magnitude of SARS-CoV-2 infection in East Java, Indonesia, we investigated the prevalence of immunoglobulin G (IgG) antibodies. We enrolled 1,819 individuals from June to December 2020 and observed that the subjects' overall prevalence of IgG antibody to SARS-CoV-2 was 11.4% (207/1,819). The prevalence of anti-SARS-CoV-2 antibodies differed significantly between the job/occupation groups (P = 0.0001). A greater prevalence of IgG was detected in laboratory technicians (who take samples from suspected cases and deal with polymerase chain reaction [PCR] procedures, 22.2%) compared to medical personnel who see and take direct care of patients with COVID-19 (e.g., physicians and nurses, 6.0%), other staff in medical facilities (2.9%), general population (12.1%) and non-COVID-19 patients (14.6%). The highest prevalence among age groups was in the 40-49-year-olds (14.8%), and the lowest prevalence was in the 20-29-year-olds (7.4%). However, the younger population still showed a higher prevalence than generally reported, suggesting greater exposure to the virus but less susceptibility to the disease. A geographical difference was also observed: a higher prevalence in Surabaya (13.1%) than in Jombang (9.9%). In conclusion, the COVID-19 outbreak among asymptomatic populations was characterized by a high prevalence of infection in East Java, Indonesia.2021, PloS one, 16(5) (5), e0251234, English, International magazine[Refereed]Scientific journal
- Most current clinical vaccines work primarily by inducing the production of neutralizing antibodies against pathogens. Vaccine adjuvants that efficiently induce T cell responses to protein antigens need to be developed. In this study, we developed a new combination adjuvant consisting of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), D35, and an aluminum salt. Among the various combinations tested, the DOTAP/D35/aluminum salt adjuvant induced strong T cell and antibody responses against the model protein antigen with a single immunization. Adjuvant component and model antigen interaction studies in vitro also revealed that the strong mutual interactions among protein antigens and other components were one of the important factors for this efficient immune induction by the novel combination adjuvant. In addition, in vivo imaging of the antigen distribution suggested that the DOTAP component in the combination adjuvant formulation elicited transient antigen accumulation at the draining lymph nodes, possibly by antigen uptake DC migration. These results indicate the potential of the new combination adjuvant as a promising vaccine adjuvant candidate to treat infectious diseases and cancers.2021, PloS one, 16(8) (8), e0254628, English, International magazine[Refereed]Scientific journal
- Human herpesvirus 6A (HHV-6A) and HHV-6B use different cellular receptors, human CD46 and CD134, respectively and have different cell tropisms although they have 90% similarity at the nucleotide level. An important feature that characterizes HHV-6A/6B is the glycoprotein H (gH)/gL/gQ1/gQ2 complex (a tetramer) that each virus has specifically on its envelope. Here, to determine which molecules in the tetramer contribute to the specificity for each receptor, we developed a cell-cell fusion assay system for HHV-6A and HHV-6B that uses the cells expressing CD46 or CD134. With this system, when we replaced the gQ1 or gQ2 of HHV-6A with that of HHV-6B in the tetramer, the cell fusion activity mediated by glycoproteins via CD46 was lower than that done with the original-type tetramer. When we replaced the gQ1 or the gQ2 of HHV-6A with that of HHV-6B in the tetramer, the cell fusion mediated by glycoproteins via CD134 was not seen. In addition, we generated two types of C-terminal truncation mutants of HHV-6A gQ2 (AgQ2) to examine the interaction domains of HHV-6A gQ1 (AgQ1) and AgQ2. We found that amino acid residues 163 to 185 in AgQ2 are important for interaction of AgQ1 and AgQ2. Finally, to investigate whether HHV-6B gQ2 (BgQ2) can complement AgQ2, an HHV-6A genome harboring BgQ2 was constructed. The mutant could not produce an infectious virus, indicating that BgQ2 cannot work for the propagation of HHV-6A. These results suggest that gQ2 supports the tetramer's function, and the combination of gQ1 and gQ2 is critical for virus propagation.IMPORTANCE Glycoprotein Q2 (gQ2), an essential gene for virus propagation, forms a heterodimer with gQ1. The gQ1/gQ2 complex has a critical role in receptor recognition in the gH/gL/gQ1/gQ2 complex (a tetramer). We investigated whether gQ2 regulates the specific interaction between the HHV-6A or -6B tetramer and CD46 or CD134. We established a cell-cell fusion assay system for HHV-6A/6B and switched the gQ1 or gQ2 of HHV-6A with that of HHV-6B in the tetramer. Although cell fusion was induced via CD46 when gQ1 or gQ2 was switched between HHV-6A and -6B, the activity was lower than that of the original combination. When gQ1 or gQ2 was switched in HHV-6A and -6B, no cell fusion was observed via CD134. HHV-6B gQ2 could not complement the function of HHV-6A's gQ2 in HHV-6A propagation, suggesting that the combination of gQ1 and gQ2 is critical to regulate the specificity of the tetramer's function for virus entry.Corresponding, Dec. 2020, Journal of virology, English, International magazine[Refereed]Scientific journal
- Glycerophospholipids are major components of cell membranes. Phosphatidylethanolamine (PE) is a glycerophospholipid that is involved in multiple cellular processes, such as membrane fusion, the cell cycle, autophagy, and apoptosis. In this study, we investigated the role of PE biosynthesis in herpes simplex virus 1 (HSV-1) infection by knocking out the host cell gene encoding phosphate cytidylyltransferase 2, ethanolamine (Pcyt2), which is a key rate-limiting enzyme in one of the two major pathways for PE biosynthesis. Pcyt2 knockout reduced HSV-1 replication and caused an accumulation of unenveloped and partially enveloped nucleocapsids in the cytoplasm of an HSV-1-infected cell culture. A similar phenotype was observed when infected cells were treated with meclizine, which is an inhibitor of Pcyt2. In addition, treatment of HSV-1-infected mice with meclizine significantly reduced HSV-1 replication in the mouse brains and improved their survival rates. These results indicated that PE biosynthesis mediated by Pcyt2 was required for efficient HSV-1 envelopment in the cytoplasm of infected cells and for viral replication and pathogenicity in vivo The results also identified the PE biosynthetic pathway as a possible novel target for antiviral therapy of HSV-associated diseases and raised an interesting possibility for meclizine repositioning for treatment of these diseases, since it is an over-the-counter drug that has been used for decades against nausea and vertigo in motion sickness.IMPORTANCE Glycerophospholipids in cell membranes and virus envelopes often affect viral entry and budding. However, the role of glycerophospholipids in membrane-associated events in viral replication in herpesvirus-infected cells has not been reported to date. In this study, we have presented data showing that cellular PE biosynthesis mediated by Pcyt2 is important for HSV-1 envelopment in the cytoplasm, as well as for viral replication and pathogenicity in vivo This is the first report showing the importance of PE biosynthesis in herpesvirus infections. Our results showed that inhibition of Pcyt2, a key cell enzyme for PE synthesis, significantly inhibited HSV-1 replication and pathogenicity in mice. This suggested that the PE biosynthetic pathway, as well as the HSV-1 virion maturation pathway, can be a target for the development of novel anti-HSV drugs.Nov. 2020, Journal of virology, 94(24) (24), English, International magazine[Refereed]Scientific journal
- BACKGROUND: The highly pathogenic avian influenza A/H5N1 virus is one of the causative agents of acute lung injury (ALI) with high mortality rate. Studies on therapeutic administration of bone marrow-derived mesenchymal stem cells (MSCs) in ALI caused by the viral infection have been limited in number and have shown conflicting results. The aim of the present investigation is to evaluate the therapeutic potential of MSC administration in A/H5N1-caused ALI, using a mouse model. METHODS: MSCs were prepared from the bone marrow of 9 to 12 week-old BALB/c mice. An H5N1 virus of A/turkey/East Java/Av154/2013 was intranasally inoculated into BALB/c mice. On days 2, 4, and 6 after virus inoculation, MSCs were intravenously administered into the mice. To evaluate effects of the treatment, we examined for lung alveolar protein as an indicator for lung injury, PaO2/FiO2 ratio for lung functioning, and lung histopathology. Expressions of NF-κB, RAGE (transmembrane receptor for damage associated molecular patterns), TNFα, IL-1β, Sftpc (alveolar cell type II marker), and Aqp5+ (alveolar cell type I marker) were examined by immunohistochemistry. In addition, body weight, virus growth in lung and brain, and duration of survival were measured. RESULTS: The administration of MSCs lowered the level of lung damage in the virus-infected mice, as shown by measuring lung alveolar protein, PaO2/FiO2 ratio, and histopathological score. In the MSC-treated group, the expressions of NF-κB, RAGE, TNFα, and IL-1β were significantly suppressed in comparison with a mock-treated group, while those of Sftpc and Aqp5+ were enhanced. Body weight, virus growth, and survival period were not significantly different between the groups. CONCLUSION: The administration of MSCs prevented further lung injury and inflammation, and enhanced alveolar cell type II and I regeneration, while it did not significantly affect viral proliferation and mouse morbidity and mortality. The results suggested that MSC administration was a promissing strategy for treatment of acute lung injuries caused by the highly pathogenic avian influenza A/H5N1 virus, although further optimization and combination use of anti-viral drugs will be obviously required to achieve the goal of reducing mortality.Nov. 2020, BMC infectious diseases, 20(1) (1), 823 - 823, English, International magazine, Co-authored internationally[Refereed]Scientific journal
- Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder, caused by mutation in the gene encoding lamin A/C, which produces a truncated protein called progerin. In cells from HGPS patients, progerin accumulates at the nuclear membrane (NM), where it causes NM deformations. In this study, we investigated whether progerin-induced NM deformation involved ESCRT-III, a protein complex that remodels nuclear and cytoplasmic membranes. The ESCRT-III protein CHMP4B was recruited to sites of aberrant NM proliferation in human cells ectopically expressing progerin and in patient-derived HGPS fibroblasts. Derepression of NM deformation in these cells was observed following depletion of CHMP4B or an ESCRT-III adaptor, ALIX. Treatment with rapamycin (which induce autophagic clearance of progerin and reverse progerin-induced cellular phenotypes) down-regulated progerin-induced NM deformation, whereas treatment with bafilomycin A1 (an inhibitor of autophagy and lysosome-based degradation) or CHMP4B depletion antagonized the effects of rapamycin. These results indicate that the ALIX-mediated ESCRT-III pathway plays a suppressive role in progerin-induced NM deformation and suggest that autophagy down-regulates progerin-induced NM deformation in a manner dependent on ESCRT-III machinery.Nov. 2020, Scientific reports, 10(1) (1), 18877 - 18877, English, International magazine[Refereed]Scientific journal
- Human herpesvirus 6A (HHV-6A) is a member of the genus Roseolovirus and the subfamily Betaherpesvirinae. It is similar to and human cytomegalovirus (HCMV). HHV-6A encodes a 41 kDa nuclear phosphoprotein, U27, which acts as a processivity factor in the replication of the viral DNA. HHV-6A U27 has 43% amino acid sequence homology with HCMV UL44, which is important for DNA replication. A previous study on HHV-6A U27 revealed that it greatly increases the in vitro DNA synthesis activity of HHV-6A DNA polymerase. However, the role of U27 during the HHV-6A virus replication process remains unclear. In this study, we constructed a U27-deficient HHV-6A mutant (HHV-6ABACU27mut) with a frameshift insertion at the U27 gene using an HHV-6A bacterial artificial chromosome (BAC) system. Viral reconstitution from the mutant BAC DNA was not detected, in contrast to the wild type and the revertant from the U27 mutant. This suggests that U27 plays a critical role in the life cycle of HHV-6A.Corresponding, Oct. 2020, Microbiology and immunology, 64(10) (10), 703 - 711, English, International magazine[Refereed]Scientific journal
- In Indonesia, the highly pathogenic avian influenza A/H5N1 virus has become endemic and has been linked with direct transmission to humans. From 2013 to 2014, we isolated avian influenza A/H5N1 and A/H3N6 viruses from poultry in Indonesia. This study aimed to reveal their pathogenicity in mammals using a mouse model. Three of the isolates, Av154 of A/H5N1 clade 2.3.2.1c, Av240 of A/H5N1 clade 2.1.3.2b, and Av39 of A/H3N6, were inoculated into BALB/c mice. To assess morbidity and mortality, we measured body weight daily and monitored survival for 20 d. Av154- and Av240-infected mice lost 25% of their starting body weight by day 7, while Av39-infected mice did not. Most of the Av154-infected mice died on day 8, while the majority of the Av240-infected mice survived until day 20. A 50% mouse lethal dose was calculated to be 2.0 × 101 50% egg infectious doses for Av154, 1.1 × 105 for Av240 and > 3.2 × 106 for Av39. The Av154 virus was highly virulent and lethal in mice without prior adaptation, suggesting its high pathogenic potential in mammals. The Av240 virus was highly virulent but modestly lethal, whereas the Av39 virus was neither virulent nor lethal. Several mammalian adaptive markers of amino acid residues were associated with the highly virulent and lethal phenotypes of the Av154 virus.Sep. 2020, Japanese journal of infectious diseases, 73(5) (5), 336 - 342, English, Domestic magazine, Co-authored internationally[Refereed]Scientific journal
- A unique glycoprotein is expressed on the virus envelope of human herpesvirus 6B (HHV-6B): the complex gH/gL/gQ1/gQ2 (hereafter referred to as the HHV-6B tetramer). This tetramer recognizes a host receptor expressed on activated T cells: human CD134 (hCD134). This interaction is essential for HHV-6B entry into the susceptible cells and is a determinant for HHV-6B cell tropism. The structural mechanisms underlying this unique interaction were unknown. Herein we solved the interactions between the HHV-6B tetramer and the receptor by using their neutralizing antibodies in molecular and structural analyses. A surface plasmon resonance analysis revealed fast dissociation/association between the tetramer and hCD134, although the affinity was high (KD = 18 nM) and comparable to those for the neutralizing antibodies (anti-gQ1: 17 nM, anti-gH: 2.7 nM). A competition assay demonstrated that the anti-gQ1 antibody competed with hCD134 in the HHV-6B tetramer binding whereas the anti-gH antibody did not, indicating the direct interaction of gQ1 and hCD134. A single-particle analysis by negative-staining electron microscopy revealed the tetramer's elongated shape with a gH/gL part and extra density corresponding to gQ1/gQ2. The anti-gQ1 antibody bound to the tip of the extra density, and anti-gH antibody bound to the putative gH/gL part. These results highlight the interaction of gQ1/gQ2 in the HHV-6B tetramer with hCD134, and they demonstrate common features among viral ligands of the betaherpesvirus subfamily from a macroscopic viewpoint.Corresponding, Jul. 2020, PLoS pathogens, 16(7) (7), e1008648, English, International magazine, Co-authored internationally[Refereed]Scientific journal
- Primary infection of human herpesvirus 6B (HHV-6B) occurs in infants after the decline of maternal immunity and causes exanthema subitum accompanied by a high fever, and it occasionally develops into encephalitis resulting in neurological sequelae. There is no effective prophylaxis for HHV-6B, and its development is urgently needed. The glycoprotein complex gH/gL/gQ1/gQ2 (called 'tetramer of HHV-6B') on the virion surface is a viral ligand for its cellular receptor human CD134, and their interaction is thus essential for virus entry into the cells. Herein we examined the potency of the tetramer as a vaccine candidate against HHV-6B. We designed a soluble form of the tetramer by replacing the transmembrane domain of gH with a cleavable tag, and the tetramer was expressed by a mammalian cell expression system. The expressed recombinant tetramer is capable of binding to hCD134. The tetramer was purified to homogeneity and then administered to mice with aluminum hydrogel adjuvant and/or CpG oligodeoxynucleotide adjuvant. After several immunizations, humoral and cellular immunity for HHV-6B was induced in the mice. These results suggest that the tetramer together with an adjuvant could be a promising candidate HHV-6B vaccine.Corresponding, Public Library of Science (PLoS), Jul. 2020, PLoS pathogens, 16(7) (7), e1008609 - e1008609, English, International magazine[Refereed]Scientific journal
- Corresponding, May 2020, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 72(4) (4), 723 - 724, English, International magazine[Refereed]Scientific journal
- Human herpesvirus 6B (HHV-6B), a T-lymphotropic virus, infects almost exclusively humans. An animal model of HHV-6B has not been available. Here, we report the first animal model to mimic HHV-6B pathogenesis; the model is based on humanized mice in which human immune cells were engrafted and maintained. For HHV-6B replication, adequate human T-cell activation (which becomes susceptible to HHV-6B) is necessary in this murine model. Here, we found that an additional transfer of human mononuclear cells to humanized mice resulted in an explosive proliferation of human activated T cells, which could be representative of graft-versus-host disease (GVHD) because the primary transfer of human cells was not sufficient to increase the number and ratio of human T cells. Mice infected with HHV-6B became weak and/or died approximately 7 to 14 days later. Quantitative PCR analysis revealed that the spleen and lungs were the major sites of HHV-6B replication in this model, and this was corroborated by the detection of viral proteins in these organs. Histological analysis also revealed the presence of megakaryocytes, indicating HHV-6B infection. Multiplex analysis of cytokines/chemokines in sera from the infected mice showed secretions of human cytokines/chemokines as reported for both in vitro infection and clinical samples, indicating that the secreted cytokines could affect pathogenesis. This is the first animal model showing HHV-6B pathogenesis, and it will be useful for elucidating the pathogenicity of HHV-6B, which is related to GVHD and idiopathic pneumonia syndrome.IMPORTANCE Human herpesvirus 6B (HHV-6B) is a ubiquitous virus that establishes lifelong latent infection only in humans, and the infection can reactivate, with severe complications that cause major problems. A small-animal model of HHV-6B infection has thus been desired for research regarding the pathogenicity of HHV-6B and the development of antiviral agents. We generated humanized mice by transplantation with human hematopoietic stem cells, and here, we modified the model by providing an additional transfer of human mononuclear cells, providing the proper conditions for efficient HHV-6B infection. This is the first humanized mouse model to mimic HHV-6B pathogenesis, and it has great potential for research into the in vivo pathogenesis of HHV-6B.Corresponding, Feb. 2020, Journal of virology, 94(6) (6), English, International magazine[Refereed]Scientific journal
- Human herpesvirus 6 (HHV-6) infects over 90% of people. The HHV-6 subtype, HHV-6B in particular, is often associated with exanthem subitum in early childhood. Exanthem subitum is usually self-limiting and good prognosis disease; however, some infants primarily infected with HHV-6B develop encephalitis/encephalopathy, and half of the patients developed encephalopathy reported to have neurological sequelae. Furthermore, after primary infection, HHV-6B remains in a latent state and sometimes reactivated in immunosuppressed patients, causing life-threatening severe encephalopathy. However, effective immunotherapies or vaccines for controlling HHV-6B infection and reactivation have not yet been established. Recently, we have found that the HHV-6B tetrameric glycoprotein (g) complex, gH/gL/gQ1/gQ2 is a promising vaccine candidate, and currently under preclinical development. To confirm our vaccine candidate protein complex induce detectable T-cell responses, in this study, we comprehensively screened CD4+ and CD8+ T-cell epitopes in the gH/gL/gQ1/gQ2 tetrameric complex protein in mice immunisation model. Both BALB/c and C57BL/6 mice were immunised with the tetrameric complex protein or plasmid DNA encoding gH, gL, gQ1, and gQ2, and then restimulated with 162 20-mer peptides covering the whole gH/gL/gQ1/gQ2 sequences; multiple CD4+ and CD8+ T-cell-stimulating peptides were identified in both BALB/c and C57BL/6 mice. Our study demonstrates that gH/gL/gQ1/gQ2 tetramer-targeted vaccination has potential to induce T-cell responses in two different strains of mice and supports the future development and application of T-cell-inducing vaccine and immunotherapies against HHV-6B.2020, Journal of immunology research, 2020, 4697529 - 4697529, English, International magazine[Refereed]Scientific journal
- Wiley, Jun. 2019, Pain Pract., 19(5) (5), 476-483. doi: 10.1111/papr.127 - 483[Refereed]Scientific journal
- Corresponding, May 2019, J Virol., 93(10) (10), 3911. doi: 10.1038/s41598-019-Humanization of Murine Neutralizing Antibodies against Human Herpesvirus 6B.[Refereed]Scientific journal
- We isolated an avian influenza A/H9N2 virus from an apparently healthy chicken at a live-poultry market in January 2018. This is the first report of a whole-genome sequence of A/H9N2 virus in Indonesia. Phylogenetic analyses indicated that intrasubtype reassortment of genome segments is involved in the genesis of the A/H9N2 virus.Apr. 2019, Microbiology resource announcements, 8(17) (17), e01671 - 18, English, International magazine[Refereed]Scientific journal
- The identification of Human herpesvirus 6B (HHV-6B) epitopes that are recognized by T-cells could contribute to the development of potential vaccines and immunotherapies. Here, we identified CD4+ and H-2Kd-restricted CD8+ T-cell epitopes on the glycoprotein Q1 of HHV-6B (BgQ1), which is a unique glycoprotein and essential for HHV-6B viral entry, by using in vivo electroporation with a plasmid DNA encoding BgQ1, overlapping peptides spanning the BgQ1 sequence, ELISPOT assay for quantification of gamma interferon (IFN-γ), and computer-based T-cell epitope prediction programs. The CD4+ and CD8+ T-cell epitopes identified in BALB/c mice in this study could be a good animal model system for use in the development of T-cell responses, inducing HHV-6B vaccines or immunotherapies.Corresponding, Mar. 2019, Scientific reports, 9(1) (1), 3911 - 3911, English, International magazine[Refereed]Scientific journal
- Characterizing complex viral transcriptomes by conventional RNA sequencing approaches is complicated by high gene density, overlapping reading frames, and complex splicing patterns. Direct RNA sequencing (direct RNA-seq) using nanopore arrays offers an exciting alternative whereby individual polyadenylated RNAs are sequenced directly, without the recoding and amplification biases inherent to other sequencing methodologies. Here we use direct RNA-seq to profile the herpes simplex virus type 1 (HSV-1) transcriptome during productive infection of primary cells. We show how direct RNA-seq data can be used to define transcription initiation and RNA cleavage sites associated with all polyadenylated viral RNAs and demonstrate that low level read-through transcription produces a novel class of chimeric HSV-1 transcripts, including a functional mRNA encoding a fusion of the viral E3 ubiquitin ligase ICP0 and viral membrane glycoprotein L. Thus, direct RNA-seq offers a powerful method to characterize the changing transcriptional landscape of viruses with complex genomes.Feb. 2019, Nature communications, 10(1) (1), 754 - 754, English, International magazine, Co-authored internationally[Refereed]Scientific journal
- Corresponding, 2019, Advances in virus research, 104, 283 - 312[Refereed]
- BACKGROUND: CD134 (OX40), which is a cellular receptor for human herpesvirus-6B (HHV-6B) and expresses on activated T cells, may play a key role for HHV-6B replication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). OBJECTIVES: Therefore, we examined the CD134 expression on T cells and HHV-6B replication after allo-HSCT, and analyzed the correlation between them. STUDY DESIGN: Twenty-three patients after allo-HSCT were enrolled. The percentages of CD134-positive cells within the CD4+ and CD8+ cell populations were measured by flow cytometry, and the viral copy number of HHV-6B was simultaneously quantified by real-time PCR. The correlation between CD134 and HHV-6B viral load was then statistically analyzed. RESULTS: HHV-6B reactivation occurred in 11 of 23 patients (47.8%). CD134 expression was seen on T cells and was coincident with the time of peak viral load. The percentage of CD134-positive cells decreased significantly when HHV-6B DNA disappeared (p = .005 in CD4+ T cells, p = .02 in CD8+ T cells). In the 4 patients who underwent umbilical cord blood transplantation (UCBT), the viral load varied with the percentage of CD134-positive cells. In the comparison between the HHV-6B reactivation group and non-reactivation group, maximum percentages of CD134-positive cells among CD4+ T cells in reactivation group were significantly higher than those in non-reactivation group (p = .04). CONCLUSIONS: This is the first study to show that a correlation of CD134 expression on T cells with HHV-6B replication after allo-HSCT, especially in UCBT. The results possibly indicate that CD134 on T cells plays a key role for HHV-6B replication after allo-HSCT.Corresponding, May 2018, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 102, 50 - 55, English, International magazine[Refereed]Scientific journal
- Varicella-zoster virus (VZV), an alphaherpesvirus, establishes lifelong latent infection in the neurons of >90% humans worldwide, reactivating in one-third to cause shingles, debilitating pain and stroke. How VZV maintains latency remains unclear. Here, using ultra-deep virus-enriched RNA sequencing of latently infected human trigeminal ganglia (TG), we demonstrate the consistent expression of a spliced VZV mRNA, antisense to VZV open reading frame 61 (ORF61). The spliced VZV latency-associated transcript (VLT) is expressed in human TG neurons and encodes a protein with late kinetics in productively infected cells in vitro and in shingles skin lesions. Whereas multiple alternatively spliced VLT isoforms (VLTly) are expressed during lytic infection, a single unique VLT isoform, which specifically suppresses ORF61 gene expression in co-transfected cells, predominates in latently VZV-infected human TG. The discovery of VLT links VZV with the other better characterized human and animal neurotropic alphaherpesviruses and provides insights into VZV latency.Mar. 2018, Nature communications, 9(1) (1), 1167 - 1167, English, International magazine[Refereed]
- Corresponding, American Society for Microbiology, Mar. 2018, Journal of Virology, 92(5) (5), English[Refereed]Scientific journal
- Human herpes virus 6 (HHV-6) is a common human pathogen that is most often detected in hematopoietic cells. Although human cells harboring chromosomally integrated HHV-6 can be generated in vitro, the availability of such cell lines originating from in vivo tissues is limited. In this study, chromosomally integrated HHV-6B has been identified in a human vascular endothelial cell line, HUV-EC-C (IFO50271), derived from normal umbilical cord tissue. Sequence analysis revealed that the viral genome was similar to the HHV-6B HST strain. FISH analysis using a HHV-6 DNA probe showed one signal in each cell, detected at the distal end of the long arm of chromosome 9. This was consistent with a digital PCR assay, validating one copy of the viral DNA. Because exposure of HUV-EC-C to chemicals did not cause viral reactivation, long term cell culture of HUV-EC-C was carried out to assess the stability of viral integration. The growth rate was altered depending on passage numbers, and morphology also changed during culture. SNP microarray profiles showed some differences between low and high passages, implying that the HUV-EC-C genome had changed during culture. However, no detectable change was observed in chromosome 9, where HHV-6B integration and the viral copy number remained unchanged. Our results suggest that integrated HHV-6B is stable in HUV-EC-C despite genome instability.Feb. 2018, Cytotechnology, 70(1) (1), 141 - 152, English, International magazine[Refereed]Scientific journal
- Oxford University Press, Feb. 2018, American Journal of Epidemiology, 187(2) (2), 251 - 259, English[Refereed]Scientific journal
- Varicella-zoster virus (VZV) is the first and only human herpesvirus for which a licensed live attenuated vaccine, vOka, has been developed. vOka has highly safe and effective profiles; however, worldwide herd immunity against VZV has not yet been established and it is far from eradication. Despite the successful reduction in the burden of VZV-related illness by the introduction of the vaccine, some concerns about vOka critically prevent worldwide acceptance and establishment of herd immunity, and difficulties in addressing these criticisms often relate to its ill-defined mechanism of attenuation. Advances in scientific technologies have been applied in the VZV research field and have contributed toward uncovering the mechanism of vOka attenuation as well as VZV biology at the molecular level. A subunit vaccine targeting single VZV glycoprotein, rationally designed based on the virological and immunological research, has great potential to improve the strategy for eradication of VZV infection in combination with vOka.2018, Advances in experimental medicine and biology, 1045, 123 - 142, English, International magazine[Refereed]
- Springer New York LLC, 2018, Advances in Experimental Medicine and Biology, 1045, 145 - 165, English[Refereed]In book
- Springer New York LLC, 2018, Advances in Experimental Medicine and Biology, 1045, 227 - 249, English[Refereed]In book
- Corresponding, Nov. 2017, JOURNAL OF VIROLOGY, 91(21) (21), English[Refereed]Scientific journal
- Jul. 2017, JOURNAL OF VIROLOGY, 91(14) (14), English[Refereed]Scientific journal
- Apr. 2017, EPIDEMIOLOGY AND INFECTION, 145(6) (6), 1270 - 1275, English[Refereed]Scientific journal
- Corresponding, Feb. 2017, JOURNAL OF MEDICAL VIROLOGY, 89(2) (2), 313 - 317, English[Refereed]Scientific journal
- Dec. 2016, JOURNAL OF INFECTIOUS DISEASES, 214(12) (12), 1929 - 1936, English[Refereed]Scientific journal
- Nov. 2016, JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 75(5) (5), 950 - +, English[Refereed]Scientific journal
- A 41-year-old female was referred to our dermatology department with generalized erythema, which had occurred after she had started to take oral carbamazepine. She had also developed a fever and cervical lymphadenopathy. As drug-induced hypersensitivity syndrome (DIHS) was suspected, she was given high-dose oral prednisolone (60mg/day). Despite corticosteroid treatment, she continued to exhibit clinical symptoms, including eruptions, hypogammaglobulinemia, and abnormal serum levels of amylase and lipase. A skin patch test with carbamazepine produced a positive result, whereas a drug-induced lymphocyte stimulation test with carbamazepine only produced a positive result in the early phase of the disease. In this case, cytomegalovirus (CMV) might have been responsible for the patient's persistent clinical symptoms because we did not detect the reactivation of human herpesvirus-6 during the patient's hospitalization, while she exhibited a continuously high anti-CMV-IgM titer.Skin Research, 15: 327-331, 2016Meeting of Osaka Dermatological Association/Meeting of Keiji Dermatological Association, Oct. 2016, 皮膚の科学, 15(5号) (5号), 327 - 331, Japanese[Refereed]Scientific journal
- Sep. 2016, JOURNAL OF INFECTION AND CHEMOTHERAPY, 22(9-10) (9-10), 593 - 598, English[Refereed]Scientific journal
- Aug. 2016, DIABETIC MEDICINE, 33(8) (8), 1094 - 1101, English[Refereed]Scientific journal
- Aug. 2016, PLOS PATHOGENS, 12(8) (8), e1005825, English[Refereed]Scientific journal
- Aug. 2016, JOURNAL OF DERMATOLOGICAL SCIENCE, 83(2) (2), 151 - 154, English[Refereed]Scientific journal
- May 2016, PLOS PATHOGENS, 12(5) (5), e1005666, English[Refereed]Scientific journal
- Corresponding, May 2016, PLOS PATHOGENS, 12(5) (5), e1005594, English[Refereed]Scientific journal
- Corresponding, Mar. 2016, VIROLOGY, 490, 1 - 5, English[Refereed]Scientific journal
- Corresponding, Feb. 2016, JOURNAL OF VIROLOGY, 90(3) (3), 1677 - 1681, English[Refereed]Scientific journal
- Corresponding, Feb. 2016, VIROLOGY, 489, 151 - 157, English[Refereed]Scientific journal
- Corresponding, Kobe University School of Medicine, 2016, Kobe Journal of Medical Sciences, 62(6) (6), E142 - E149, EnglishPurification, crystallization and X-ray diffraction study of the C-terminal domain of human herpesvirus 6A immediate early protein 2[Refereed]Scientific journal
- 2016, MOLECULAR AND CELLULAR LIFE SCIENCES: INFECTIOUS DISEASES, BIOCHEMISTRY AND STRUCTURAL BIOLOGY 2015 CONFERENCE, 18, 205 - 212, English[Refereed]International conference proceedings
- Jan. 2016, 医薬ジャーナル, 52(増刊) (増刊), 313 - 315, Japanese【新薬展望2016】 (第III部)治療における最近の新薬の位置付け＜薬効別＞ 新薬の広場 ワクチン 水痘ワクチン[Refereed]Scientific journal
- Jan. 2016, LARYNGOSCOPE, 126(1) (1), E35 - E39, English[Refereed]Scientific journal
- Corresponding, Nov. 2015, VACCINE, 33(45) (45), 6085 - 6092, English[Refereed]Scientific journal
- Corresponding, Oct. 2015, JOURNAL OF VIROLOGY, 89(19) (19), 10125 - 10129, English[Refereed]Scientific journal
- Sep. 2015, JOURNAL OF DERMATOLOGICAL SCIENCE, 79(3) (3), 235 - 240, English[Refereed]Scientific journal
- Corresponding, Sep. 2015, PLOS ONE, 10(9) (9), e0137420, English[Refereed]Scientific journal
- Aug. 2015, JOURNAL OF BIOLOGICAL CHEMISTRY, 290(32) (32), 19833 - 19843, English[Refereed]Scientific journal
- Corresponding, May 2015, JOURNAL OF VIROLOGY, 89(9) (9), 5159 - 5163, English[Refereed]Scientific journal
- Mar. 2015, JOURNAL OF VIROLOGY, 89(5) (5), 2615 - 2627, English[Refereed]Scientific journal
- 2015, JOURNAL OF EPIDEMIOLOGY, 25(10) (10), 617 - 625, English[Refereed]Scientific journal
- Corresponding, Jan. 2015, MICROBIOLOGY AND IMMUNOLOGY, 59(1) (1), 48 - 53, English[Refereed]Scientific journal
- Corresponding, Dec. 2014, JOURNAL OF GENERAL VIROLOGY, 95(Pt 12) (Pt 12), 2769 - 2777, English[Refereed]Scientific journal
- Dec. 2014, PLOS ONE, 9(12) (12), e113962, English[Refereed]Scientific journal
- Nov. 2014, JOURNAL OF GENERAL VIROLOGY, 95(Pt 11) (Pt 11), 2365 - 2371, English[Refereed]Scientific journal
- Nov. 2014, ANTIVIRAL RESEARCH, 111, 69 - 77, English[Refereed]Scientific journal
- Oct. 2014, INTERNATIONAL JOURNAL OF PHARMACEUTICS, 473(1-2) (1-2), 113 - 125, English[Refereed]Scientific journal
- Corresponding, Sep. 2014, JOURNAL OF VIROLOGY, 88(18) (18), 10875 - 10882, English[Refereed]Scientific journal
- May 2014, ARCHIVES OF VIROLOGY, 159(5) (5), 863 - 870, English[Refereed]
- Apr. 2014, AAPS PHARMSCITECH, 15(2) (2), 317 - 325, English[Refereed]Scientific journal
- Corresponding, Feb. 2014, Microbiology and immunology, 58(2) (2), Februarycover[Refereed]
- Corresponding, Feb. 2014, MICROBIOLOGY AND IMMUNOLOGY, 58(2) (2), 119 - 125, English[Refereed]Scientific journal
- Corresponding, Feb. 2014, VIROLOGY, 450, 98 - 105, English[Refereed]Scientific journal
- Corresponding, Jan. 2014, MICROBIOLOGY AND IMMUNOLOGY, 58(1) (1), 22 - 30, English[Refereed]Scientific journal
- Corresponding, Jan. 2014, JOURNAL OF VIROLOGY, 88(1) (1), 188 - 201, English[Refereed]Scientific journal
- Corresponding, Oct. 2013, MICROBIOLOGY AND IMMUNOLOGY, 57(10) (10), 704 - 714, English[Refereed]Scientific journal
- Sep. 2013, JOURNAL OF INFECTION, 67(3) (3), 215 - 219, English[Refereed]Scientific journal
- Jul. 2013, Clinical and Vaccine Immunology, 20(7) (7), 998 - 1007, English[Refereed]Scientific journal
- Corresponding, Jun. 2013, JOURNAL OF VIROLOGY, 87(12) (12), 7054 - 7063, English[Refereed]Scientific journal
- Corresponding, May 2013, Proceedings of the National Academy of Sciences of the United States of America, 110(22) (22), 9096 - 9099, English[Refereed]Scientific journal
- Apr. 2013, EPIDEMIOLOGY AND INFECTION, 141(4) (4), 706 - 713, English[Refereed]Scientific journal
- Mar. 2013, JOURNAL OF DERMATOLOGICAL SCIENCE, 69(3) (3), 243 - 249, English[Refereed]Scientific journal
- Dec. 2012, ANTIVIRAL RESEARCH, 96(3) (3), 344 - 352, English[Refereed]Scientific journal
- Oct. 2012, JOURNAL OF VIROLOGY, 86(19) (19), 10695 - 10703, English[Refereed]Scientific journal
- Oct. 2012, VIRAL IMMUNOLOGY, 25(5) (5), 433 - 439, English[Refereed]Scientific journal
- Corresponding, Sep. 2012, JOURNAL OF CLINICAL VIROLOGY, 55(1) (1), 46 - 50, English[Refereed]Scientific journal
- Aug. 2012, JOURNAL OF CLINICAL IMMUNOLOGY, 32(4) (4), 690 - 697, English[Refereed]Scientific journal
- Corresponding, Aug. 2012, JOURNAL OF VIROLOGY, 86(16) (16), 8492 - 8498, English[Refereed]Scientific journal
- Jul. 2012, CLINICAL AND VACCINE IMMUNOLOGY, 19(7) (7), 979 - 990, English[Refereed]Scientific journal
- Corresponding, Jul. 2012, VIROLOGY, 429(1) (1), 21 - 28, English[Refereed]Scientific journal
- May 2012, REVIEWS IN MEDICAL VIROLOGY, 22(3) (3), 144 - 155, EnglishScientific journal
- Apr. 2012, VIROLOGY, 425(2) (2), 95 - 102, English[Refereed]Scientific journal
- Mar. 2012, JOURNAL OF EPIDEMIOLOGY, 22(2) (2), 167 - 174, English[Refereed]Scientific journal
- Corresponding, 2012, Advances in Virology, 2012, 384069, English[Refereed]
- Jan. 2012, CLINICAL AND VACCINE IMMUNOLOGY, 19(1) (1), 17 - 22, EnglishScientific journal
- Dec. 2011, JOURNAL OF VIROLOGY, 85(24) (24), 12962 - 12971, English[Refereed]Scientific journal
- Nov. 2011, JOURNAL OF VIROLOGY, 85(21) (21), 11121 - 11130, English[Refereed]Scientific journal
- 2011, Virology Journal, 8, English[Refereed]Scientific journal
- Dec. 2010, JOURNAL OF VIROLOGY, 84(24) (24), 12703 - 12712, English[Refereed]Scientific journal
- Nov. 2010, VIROLOGY, 407(2) (2), 360 - 367, English[Refereed]Scientific journal
- Sep. 2010, VIROLOGY, 405(2) (2), 280 - 288, English[Refereed]Scientific journal
- Jul. 2010, FUTURE MICROBIOLOGY, 5(7) (7), 1015 - 1023, English[Refereed]Scientific journal
- Jun. 2010, VIROLOGY, 402(1) (1), 215 - 221, English[Refereed]Scientific journal
- Apr. 2010, JOURNAL OF VIROLOGY, 84(7) (7), 3488 - 3502, EnglishScientific journal
- 2010, VARICELLA-ZOSTER VIRUS, 342, 147 - 154, English[Refereed]In book
- Jan. 2010, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 107(2) (2), 866 - 871, EnglishScientific journal
- Nov. 2009, JOURNAL OF INFECTIOUS DISEASES, 200(10) (10), 1606 - 1610, EnglishScientific journal
- Sep. 2009, VACCINE, 27(42) (42), 5896 - 5905, EnglishScientific journal
- Aug. 2009, VIROLOGY JOURNAL, 6, EnglishScientific journal
- Jul. 2009, CELLULAR MICROBIOLOGY, 11(7) (7), 1001 - 1006, English[Refereed]Scientific journal
- Mar. 2009, VIROLOGY, 385(2) (2), 294 - 302, English[Refereed]Scientific journal
- 2009, Drug Delivery System, 24(6) (6), 592 - 598, Japanese[Refereed]Scientific journal
- (株)全日本病院出版会, Dec. 2008, Derma., (147) (147), 83 - 88, Japanese【ヘルペス感染症 その診断と治療】HHV-7関連皮膚疾患の診断と治療[Refereed]
- Nov. 2008, Journal of Infectious Diseases, 198(9) (9), 1327 - 1333, English[Refereed]Scientific journal
- Nov. 2008, JOURNAL OF INFECTIOUS DISEASES, 198(9) (9), 1327 - 1333, English[Refereed]Scientific journal
- Oct. 2008, TRAFFIC, 9(10) (10), 1728 - 1742, English[Refereed]Scientific journal
- Sep. 2008, VIROLOGY, 378(2) (2), 265 - 271, English[Refereed]Scientific journal
- Aug. 2008, VIROLOGY, 377(2) (2), 289 - 295, English[Refereed]Scientific journal
- Apr. 2008, VIROLOGY JOURNAL, 5, English[Refereed]Scientific journal
- Jan. 2008, BLOOD, 111(1) (1), 320 - 327, English[Refereed]Scientific journal
- Jan. 2008, VACCINE, 26(5) (5), 589 - 594, English[Refereed]Scientific journal
- Herpesvirus entry into host cells occurs by recognition of specific cellular receptor(s) with viral envelope glycoproteins. Nucleocapsids formed in nucleus are released into cytoplasm, and acquire tegument proteins there. Nucleocapsids with tegument proteins bud into intracellular vesicles formed in infected cells, which are thought to be derived from Golgi apparatus, trans-Golgi network or endosomes. However, the precise mechanisms involved in virus final envelopment are poorly understood. Here, I review our current knowledge regarding herpesvirus entry into host cells and virus assembly.The Japanese Society for Virology, Dec. 2007, Uirusu, 57(2) (2), 151 - 158, Japanese
- Dec. 2007, VACCINE, 25(52) (52), 8741 - 8755, English[Refereed]Scientific journal
- Nov. 2007, JOURNAL OF VIROLOGY, 81(22) (22), 12654 - 12665, English[Refereed]Scientific journal
- Nov. 2007, VACCINE, 25(49) (49), 8270 - 8278, English[Refereed]Scientific journal
- Oct. 2007, Journal of virology, Vol. 82, No. 2, pp. 795-804, English[Refereed]Scientific journal
- Jun. 2007, Vaccine, 25(27) (27), 5006 - 5012, English[Refereed]Scientific journal
- May 2007, JOURNAL OF GENERAL VIROLOGY, 88, 1415 - 1422, English[Refereed]Scientific journal
- May 2007, Journal of General Virology, 88(5) (5), 1423 - 1428, English[Refereed]Scientific journal
- Mar. 2006, JOURNAL OF GENERAL VIROLOGY, 87, 501 - 508, English[Refereed]Scientific journal
- Feb. 2006, JOURNAL OF GENERAL VIROLOGY, 87, 277 - 285, English[Refereed]Scientific journal
- Oct. 2005, Journal of Virology, 79(20) (20), 13037 - 13046, EnglishScientific journal
- Sep. 2004, Vaccine, 22(29-30) (29-30), 4069 - 4074, English[Refereed]Scientific journal
- Aug. 2004, JOURNAL OF VIROLOGY, 78(15) (15), 7969 - 7983, English[Refereed]Scientific journal
- May 2004, Journal of Virology, 78(9) (9), 4609 - 4616, EnglishScientific journal
- p53 plays an important role in tumour suppression in cells exposed to some genotoxic stresses. We found that the p53 protein level was increased in a variety of cell lines infected with human herpesvirus 6 (HHV-6). Because the elevation in p53 began very soon after infection (4 h) and did not occur with UV-inactivated virus infection, it appeared to require the expression of one or more viral immediate-early (IE) genes. To elucidate the mechanism of p53 induction, we investigated its regulation at the protein level. Pulse-chase analysis showed that the stability of p53 increased in HHV-6-infected cells. In addition, the ubiquitination of p53 decreased after infection, indicating that the stability of p53 was increased through deubiquitination. We showed by confocal microscopy that the additional p53 mainly localized to the cytoplasm and that p53 was retained in the cytoplasm even after UV irradiation, but that it translocated into the nucleus in mock-infected cells. Furthermore, DNA fragmentation analysis, a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) assay and annexin V staining showed that infected cells were resistant to UV-induced apoptosis. These results lead us to propose that HHV-6 has a mechanism for retaining p53 within the cytoplasm and protects the infected cells from apoptosis.Apr. 2004, The Journal of general virology, 85(Pt 4) (Pt 4), 869 - 879, English, International magazine[Refereed]Scientific journal
- Apr. 2003, Journal of Virology, 77(8) (8), 4992 - 4999, English[Refereed]Scientific journal
- Feb. 2003, JOURNAL OF VIROLOGY, 77(4) (4), 2452 - 2458, English[Refereed]Scientific journal
- American Society for Microbiology, 2002, Journal of Virology, 76(22) (22), 11447 - 11459, English[Refereed]Scientific journal
- 2002, Journal of Virology, 76(13) (13), 6750 - 6761, English[Refereed]Scientific journal
- Society for General Microbiology, 2002, Journal of General Virology, 83(4) (4), 847 - 854, English[Refereed]Scientific journal
- 2000, Japanese Journal of Clinical Immunology, 23(6) (6), 586 - 590, English[Refereed]Scientific journal
- 2000, Journal of Virology, 74(13) (13), 6096 - 6104, English[Refereed]Scientific journal
- 2000, Journal of Medical Virology, 61(3) (3), 332 - 335, English[Refereed]Scientific journal
- 2000, Journal of Virology, 74(6) (6), 2867 - 2875, EnglishScientific journal
- Mar. 1999, Journal of Human Virology, 2(2) (2), 63 - 71, EnglishIdentification and characterization of human herpesvirus 8 open reading frame K9 viral interferon regulatory factor by a monoclonal antibody[Refereed]Scientific journal
- Academic Press Inc., Sep. 1998, Virology, 249(1) (1), 129 - 139, English[Refereed]Scientific journal
- Apr. 1998, Pediatric Infectious Disease Journal, 17(4) (4), 345 - 348, English[Refereed]Scientific journal
- Mar. 2019, 臨床とウイルス, 47(1) (1), JapaneseHHV-6宿主レセプター[Refereed][Invited]Introduction scientific journal
- Jan. 2019, 感染症, 49(1) (1)ヒトヘルペスウイルス6（HHV-6)感染症[Refereed][Invited]
- Elsevier Ltd, 04 Jan. 2016, Vaccine, 34(2) (2), 296 - 298, English[Refereed]Book review
- Aug. 2015, 化学療法の領域, 31(9号) (9号), 1807 - 1815, Japanese【持続感染・潜伏感染の機序と病態】 水痘・帯状疱疹ウイルスの潜伏と再活性化の機構Introduction scientific journal
- Apr. 2015, 感染 炎症 免疫, 57 - 59, Japanese第39回ﾍﾙﾍﾟｽｳｲﾙｽﾜｰｸｼｮｯﾌﾟ：IHW史に刻まれたアジア初日本での開催(神戸市神戸国際展示場)Introduction scientific journal
- (株)臨床医薬研究協会, Oct. 2014, 臨床医薬, 30(10) (10), 905 - 915, Japanese帯状疱疹疫学調査 水痘抗原「ビケン」を用いた皮内検査による帯状疱疹および帯状疱疹後神経痛のリスク評価 コミュニティベースの前方視的コホート研究
- 最新医学社, Apr. 2014, 最新医学, 69(4号) (4号), 810 - 818, Japanese【次世代型感染症ワクチン】 グローバル感染症 多価生ワクチン 現行の水痘生ワクチンをベースとしてIntroduction other
- 2014, 日本ウイルス学会学術集会プログラム・抄録集, 62nd組換え水痘ウイルスのルシフェラーゼ活性による増殖能の評価について
- 2014, 日本ワクチン学会学術集会プログラム・抄録集, 18thモルモットにおけるRSウイルス抗原発現組換え水痘ワクチンウイルスのワクチン効果について
- 2013, 日本ワクチン学会学術集会プログラム・抄録集, 17thRSウイルスのF抗原を発現する組換え水痘ワクチンの作製とその有効性の検討
- 31 Oct. 2012, 日本ウイルス学会学術集会プログラム・抄録集, 60th, 263, Japaneseパンデミックインフルエンザの発生に即応した,ワクチン製造用種ウイルス株の作出―インフルエンザウイルスライブラリーの利用―
- 01 Mar. 2012, 臨床とウイルス, 40(1) (1), 75 - 81, JapaneseHuman herpesvirus 6
- 2012, 日本ワクチン学会学術集会プログラム・抄録集, 16thムンプスウイルスの抗原遺伝子を有する組換え水痘ワクチン開発のための応用研究
- 2012, 日本ワクチン学会学術集会プログラム・抄録集, 16th, 140, Japanese抗インフルエンザIgAモノクローナル抗体による交叉防御効果の性状解析
- 21 Nov. 2011, 日本ワクチン学会学術集会プログラム・抄録集, 15th, 82, Japaneseインフルエンザ不活化全粒子ワクチンの経鼻接種による交叉防御効果の範囲と抗ウイルス中和抗体との関連性
- 21 Nov. 2011, 日本ワクチン学会学術集会プログラム・抄録集, 15th, 84, Japanese抗インフルエンザIgAモノクローナル抗体による交叉防御効果の可能性
- Apr. 2011, Pharma Medica, 29巻, 4, pp. 23-30, Japanese【話題の感染症とワクチン開発】 ウイルスベクターと多価ワクチン開発Introduction scientific journal
- Mar. 2011, 臨床とウイルス, 39巻, 1号, pp. 94-102, Japanese【ウイルス感染と免疫異常】 ヘルペスウイルス とくにヒトヘルペスウイルス6についてIntroduction scientific journal
- Feb. 2011, 実験医学, 29巻, 3号, pp. 379-384, Japanese【ヒトの誕生・老化・疾患を運ぶエクソソーム miRNA・タンパク質を輸送する細胞外小胞】 エクソソーム分泌経路を介したヒトヘルペスウイルス6の増殖戦略Introduction scientific journal
- [Human herpesvirus-6 and human herpesvirus-7 (HHV-6, HHV-7)].human herpesvirus 6 (HHV-6) is the major causative agent of exanthem subitum which is one of popular diseases in infant, and establishes latent infections in adults of more than 90%. Recently, the encephalitis caused by reactivated- HHV-6 has been shown in patients after transplantation. In addition, the relationship HHV-6 and drug-induced hypersensitivity syndrome has also been reported. human herpesvirus 7 (HHV-7) was isolated from the stimulated-peripheral blood lymphocytes of a healthy individual, and also causes exanthema subitum. Both viruses are related viruses which belong to betaherpesvirus subfamily, and replicate and produce progeny viruses in T cells.Dec. 2010, Uirusu, 60(2) (2), 221 - 35, Japanese, Domestic magazine
- 2010, 日本ワクチン学会学術集会プログラム・抄録集, 14th風疹ウイルス構造タンパクを発現する組換え水痘ワクチンの作製
- 2010, 日本ワクチン学会学術集会プログラム・抄録集, 14th細胞融合を抑制したムンプスウイルスhemagglutinin-neuraminidase及びfusion protein発現組換え水痘ワクチンの開発
- 2010, 日本ワクチン学会学術集会プログラム・抄録集, 14thインフルエンザ不活化全粒子ワクチン経鼻接種による交叉防御免疫応答の検討
- Nov. 2009, 臨床と微生物, 36(6) (6), 69 - 73, Japanese帯状疱疹ワクチン開発に向けた取り組み．[Invited]Introduction commerce magazine
- Mar. 2009, 解剖学雑誌, 84(Supplement) (Supplement), 195, Japaneseヒトヘルペスウイルス6粒子はエクソソーム経路を経て細胞外に放出される
- 三井住友海上福祉財団, 2009, 研究結果報告書集 : 交通安全等・高齢者福祉, 15, 137 - 140, Japanese高齢者における免疫賦活によるウイルス感染症予防の研究
- 日本組織細胞化学会, 2009, 日本組織細胞化学会総会・学術集会講演プログラム・予稿集, 50th(50) (50), 68 - 68, Japaneseヒトヘルペスウイルス6粒子のエクソソーム経路を利用した細胞外への放出機構について
- Sep. 2008, Medical Science Digest, 34(10) (10), 436 - 439, Japanese水痘生ワクチンを用いた組換えウイルスの作製と組換え多価生ワクチンとしての応用．[Invited]Introduction commerce magazine
- (一社)日本細胞生物学会, Jun. 2008, 日本細胞生物学会大会講演要旨集, 60回, 165 - 165, Englishヒトヘルペスウイルス6感染によって誘導されるmultivesicular body形成とその意義(Human herpesvirus-6 induces MVB formation and virus egress occurs via an exosomal release pathway)
- (一社)日本細胞生物学会, Jun. 2008, 日本細胞生物学会大会講演要旨集, 60回, 83 - 83, Englishメンブレントラフィックの分子機構と細胞機能 ヒトヘルペスウイルス6感染によって誘導されるmultivesicular body形成とその意義(Membrane traffic: from proteins/lipids to cells Human herpesvirus-6 induces MVB formation and virus egress occurs via an exosomal release pathway)
- 社団法人 日本農芸化学会, Jan. 2008, 化学と生物, 46(1) (1), 12 - 16, Japanese[Refereed][Invited]Introduction scientific journal
- 2006, Perspectives in Medical Virology, 12, 47 - 57, EnglishBook review
- 2005, 日本ウイルス学会学術集会プログラム・抄録集, 53rd水痘帯状疱疹ウイルスワクチン株の分子学的性状解析
- 2004, 日本ワクチン学会学術集会プログラム・抄録集, 8th水痘帯状ほう疹ウイルスの組換えウイルスの作製
- 2004, 日本ウイルス学会学術集会プログラム・抄録集, 52ndBACベクターを用いた組換え水痘帯状疱疹ウイルスの作成
- Human interleukin-6 induces human herpesvirus-8 replication in a body cavity-based lymphoma cell line.Human herpesvirus-8 (HHV-8) is etiologically associated with Kaposi's sarcoma (KS), body cavity-based lymphoma (BCBL), and multicentric Castleman's disease (MCD). These HHV-8-associated diseases arise predominantly in acquired immunodeficiency syndrome (AIDS) patients. Human interleukin-6 (huIL-6) elevated in the serum of AIDS patients is suggested to stimulate the growth of KS and BCBL and to augment the symptoms of MCD. To determine whether huIL-6 stimulates HHV-8 replication directly, expression of the HHV-8 ORF-50 immediate-early gene (transcription activator) and ORF-26 late lytic gene (a capsid protein) was assessed in a BCBL-1 cell line stimulated by huIL-6 by means of real-time reverse transcription-polymerase chain reaction. huIL-6 induced both ORF-50 and ORF-26 expression, and the maximal ORF-50 expression appeared earlier than that of ORF-26. The data indicate that huIL-6 reactivates HHV-8 in BCBL-1 cells through inducing ORF-50. We also confirmed the previously reported activities of HHV-8-encoded huIL-6 homologue (viral interleukin-6 [vIL-6]) on human immunodeficiency virus (HIV) replication in U1 cell line and huIL-6 production by MT-4 T cells, and utilizing monoclonal antibodies to the huIL-6 receptor components, we elucidated that gp130 is the signaling molecule necessary for these vIL-6 activities. These data suggest the possible existence of interaction between HIV and HHV-8 via IL-6, and that the blockade of IL-6 signal by anti-IL-6R antibody or anti-gp130 antibody can constitute a strategy to treat HIV/HHV-8 dually infected patients.Nov. 2002, Journal of medical virology, 68(3) (3), 404 - 11, English, International magazine
- Oct. 1999, JOURNAL OF VIROLOGY, 73(10) (10), 8053 - 8063, EnglishComparison of the complete DNA sequences of human herpesvirus 6 variants A and B
- Sep. 1999, JOURNAL OF HUMAN VIROLOGY, 2(5) (5), 319 - 319, EnglishIdentification and characterization of human herpesvirus 8 (HHV-8) ORF k9 viral interferon regulatory factor (vIRF) by a monoclonal antibody (vol 2, pg 63, 1999)Others
- 裳華房, Feb. 1999, 遺伝, 53(2) (2), 33 - 36, Japanese新しい潜伏性・再活性化ウイルス--ヘルペスウイルス感染症 (特集 エマージングウイルス感染症--人類の新たな脅威となるウイルス病)
- 中山書店, Aug. 1998, 免疫, (1998) (1998), 226 - 233, JapaneseKaposi肉腫関連ヘルペスウイルス(ヘルペスウイルス8) (免疫系の制御とその異常)
- Joint work, Lippincott Williams＆Wilkins, 2013Fields Virology sixth edition Human herpesviruses 6 and 7
- Joint work, 羊土社, Nov. 2011, Japaneseはじめの一歩のイラスト感染症・微生物学 / 4章 ウイルス(1,2,5,6)Scholarly book
- Joint work, 中山書店, May 2011, Japanese皮膚科臨床アセット3 ウイルス性皮膚疾患ハンドブック / HHV-7関連皮膚疾患Scholarly book
- Joint work, 日本ウイルス学会, Dec. 2010, Japaneseウイルス / ヒトヘルペスウイルス6とヒトヘルペスウイルス7(HHV-6,HHV-7)Scholarly book
- Joint work, 株式会社シーエムシー出版, Sep. 2010, Japanese次世代ワクチンの産業応用技術 / 水痘弱毒性ワクチンOka株(Okaワクチン株の臨床への応用に関して)Scholarly book
- Joint work, 日本ＤＤＳ学会, 2009, JapaneseDrug Delivery System / 組み換え水痘ウイルスを用いた多価ワクチン開発の研究Scholarly book
- Joint work, ASM PRESS, 2009, EnglishClinical Virology third edition / Human Herpesvirus 6 and Human Herpesvirus 7Scholarly book
- Joint work, 全日本病院出版会, Dec. 2008, JapaneseDerma. / HHV-7 関連皮膚疾患の診断と治療Scholarly book
- Joint work, 日本農芸化学会会誌 学会出版センター, 2008, Japanese化学と生物 / 新しい多価ワクチンの作製法. 水痘弱毒生ワクチンのベクターとしての応用Scholarly book
- Joint work, ニューサイエンス社, 2008, JapaneseMedical Science Digest / 水痘生ワクチンを用いた組換えウイルスの作製と組換え多価生ワクチンとしての応用Scholarly book
- 11th International Conference on HHV-6&7, Jun. 2019, EnglishBasic study for vaccine development of HHV-6[Invited]
- 全国ダイバーシティネットワーク 北海道ブロック会議シンポジウム, Mar. 2019, Japanese, Domestic conference研究者への道のりとこれから －後進の育成[Invited]Nominated symposium
- 第22回日本ワクチン学会学術集会, Dec. 2018, Japanese, Domestic conference水痘ワクチンウイルスをベクターとした組換え生ワクチンの開発[Invited]Nominated symposium
- 第48回日本皮膚免疫アレルギー学会総会学術大会, Nov. 2018, Japanese, Domestic conferenceヒトヘルペスウイルス6B 宿主受容体発見までの軌跡と新たな展開[Invited]Public discourse
- 第66回日本ウイルス学会学術集会, Oct. 2018, English, Domestic conferenceIdentification of the functional domain of HHV-6 glycoprotein Q2 responsible for receptor recognition
- 第66回日本ウイルス学会学術集会, Oct. 2018, English, Domestic conferenceMolecular interaction of a human herpesvirus 6B glycoprotein complex with a host receptor and neutralizing antibodies
- 第66回日本ウイルス学会学術集会, Oct. 2018, English, Domestic conferenceInternational spreading of influenza A(H1N1)pdm09 virus by the Hajji returnees
- 第66回日本ウイルス学会学術集会, Oct. 2018, English, Domestic conferenceHumanization of the neutralizing antibodies against human herpesvirus 6B
- 第66回日本ウイルス学会学術集会, Oct. 2018, EnglishEvolution of avian influenza A(H5N1)viruses from poultry in Indonesia
- 第66回日本ウイルス学会学術集会, Oct. 2018, EnglishIsolation of avian influenza A(H4N6)viruses from ducks at a live-poultry market in Indonesia
- 日本ウイルス学会学術集会, Oct. 2018, EnglishIsolation and identification of avian influenza viruses from apparently healthy ducks at a live-poultry market in Indonesia
- 第66回日本ウイルス学会学術集会, Sep. 2018, English, Domestic conferenceComparison of pathogenicity in mice between A(H5N1)isolates of Indonesian and Eurasian lineages
- The 12th China-Japan International Conference of Virology, May 2018, EnglishHHV-6B and its receptor usage
- The 2nd International Joint Symposium in Honolulu 2018, Mar. 2018, English, The 2nd International Joint Symposium in Honolulu 2018, ホノルル, アメリカ, International conferenceCell-cell fusion induced by human herpesvirus-6B(HHV-6B)[Invited]Nominated symposium
- 第21回日本ワクチン学会学術集会, Dec. 2017, Japanese, 第21回日本ワクチン学会学術集会, 福岡, Domestic conferenceヒトヘルペスウイルス6B（HHV-6B)糖タンパク質複合体の感染防御免疫誘導の解析Oral presentation
- 第21回日本ワクチン学会学術集会, Dec. 2017, Japanese, 第21回日本ワクチン学会学術集会, 福岡, Domestic conferenceヒトヘルペスウイルス6B(HHV-6B)に対する新規ワクチン開発の試みInvited oral presentation
- 姫路市医師会臨床検査センター学術講演会, Nov. 2017, Japanese, 一般社団法人 姫路市医師会, 姫路, Domestic conference「ヘルペスウイルス感染症」 ～最新情報と臨床検査の応用～[Invited]Public discourse
- 第42回 COST （Cornea Ocularsurface Seminar in Tokyo), Nov. 2017, Japanese, 第42回 COST （Cornea Ocularsurface Seminar in Tokyo), 千代田区(東京都), Domestic conference「ヒトヘルペスウイルス6感染症」[Invited]Invited oral presentation
- 2017年度COI学術講演会, Oct. 2017, Japanese, 2017年度COI（Core-Network of Ocular Infection)学術講演会, 大阪, Domestic conferenceヒトヘルペスウイル6の感染機構Invited oral presentation
- 第65回日本ウイルス学会学術集会, Oct. 2017, English, 第65回日本ウイルス学会各術集会学術事務局, 大阪, Domestic conferenceVirus Identification of pediatric viral pneumonia in Dr. Soetomo Hospital, Surabaya, Indonesiaインドネシアにおけるウイルス性小児肺炎のウイルス同定Poster presentation
- 第65回日本ウイルス学会学術集会, Oct. 2017, English, 第65回日本ウイルス学会各術集会学術事務局, 大阪, Domestic conferenceThe ubiquitin ligase regulation mechanism conserved among herpesviruses.ペルペスウイルスに共通した宿主ユビキチンリガーゼ制御機構Poster presentation
- 第65回日本ウイルス学会学術集会, Oct. 2017, English, 第65回日本ウイルス学会各術集会学術事務局, 大阪, Domestic conferenceStructural analysis of human herpesvirus 6A immediate early protein 2 C-terminal domainOral presentation
- 第65回日本ウイルス学会学術集会, Oct. 2017, English, 第65回日本ウイルス学会各術集会学術事務局, 大阪, Domestic conferencePrevalence of avian influenza virus H3N6 in poultry at a wet market in the East JavaOral presentation
- 第65回日本ウイルス学会学術集会, Oct. 2017, English, 第65回日本ウイルス学会各術集会学術事務局, 大阪, Domestic conferencePotential therapeutic role of bone marrow-derived mesenchymal stem cell in acute lung injury by highly pathogenic avian influenza virus H5N1高病原性鳥インフルエンザウイルスH5N1による急性肺損傷に対する骨髄由来間葉系幹細胞治療の可能性Poster presentation
- 第65回日本ウイルス学会学術集会, Oct. 2017, English, 第65回日本ウイルス学会各術集会学術事務局, 大阪, Domestic conferenceNovel varicella-zoster virus latency transcript inhibits viral replicationOral presentation
- 第65回日本ウイルス学会学術集会, Oct. 2017, English, 第65回日本ウイルス学会各術集会学術事務局, 大阪, Domestic conferenceInfluenza virus infections among returning Hajj and Umrah pilgrims, IndonesiaOral presentation
- 第65回日本ウイルス学会学術集会, Oct. 2017, English, 第65回日本ウイルス学会各術集会学術事務局, 大阪, Domestic conferenceHuman herpesvirus 6A/B-pathogenesis and prevention-[Invited]Nominated symposium
- 第65回日本ウイルス学会学術集会, Oct. 2017, English, 第65回日本ウイルス学会各術集会学術事務局, 大阪, Domestic conferenceHHV-6B envelope glycoprotein complex, gH/gL/gQ1/gQ2 is a key player for virus-induced cell fusion[Invited]Oral presentation
- 第65回日本ウイルス学会学術集会, Oct. 2017, English, 第65回日本ウイルス学会各術集会学術事務局, 大阪, Domestic conferenceEpidemiology and phylogenetic analysis of seasonal influenza viruses in IndonesiaOral presentation
- 第65回日本ウイルス学会学術集会, Oct. 2017, English, 第65回日本ウイルス学会各術集会学術事務局, 大阪, Domestic conferenceCoinfection of seasonal and avian influenza viruses in human in IndonesiaOral presentation
- 第65回日本ウイルス学会学術集会, Oct. 2017, English, 第65回日本ウイルス学会各術集会学術事務局, 大阪, Domestic conferenceAnalysis of the immune response by human herpesvirus-6B glycoprotein complexOral presentation
- 42nd Annual International Herpesvirus Workshop, Aug. 2017, English, IHW2017, ゲント, ベルギー, International conferenceIdentification of a novel varicella-zoster virus latency transcript that represses expression of the viral ORF61 regulatory gene[Invited]Oral presentation
- 42nd Annual International Herpesvirus Workshop, Aug. 2017, English, IHW2017, ゲント, ベルギー, International conferenceHHV-6A immediate early protein 2 shows the similarity with EBNA1 and LANA in its C-terminal domainOral presentation
- 42nd Annual International Herpesvirus Workshop, Aug. 2017, English, IHW2017, ゲント, ベルギー, International conferenceAn Allele Selection within ORF31 Gene Which Encodes Glycoprotein B, Which Occurred During Production of the Varicella-Zoster Virus Vaccine, Contributes to Its AttenuationPoster presentation
- 10th International Conference on HHV-6&7, Jul. 2017, English, 10th International Conference on HHV-6&7, ベルリン, ドイツ, International conferenceThe gH/gL/gQ1/gQ2 complex could induce protective immunity for HHV-6B[Invited]Oral presentation
- 10th International Conference on HHV-6&7, Jul. 2017, English, 10th International Conference on HHV-6&7, ベルリン, ドイツ, International conferenceStructure-based analysis of human herpesvirus 6A immediate early protein 2[Invited]Oral presentation
- 10th International Conference on HHV-6&7, Jul. 2017, English, 10th International Conference on HHV-6&7, ベルリン, ドイツ, International conferenceRole of the tyrosine-based motif in the cytoplasmic tail of the HHV-6A glycoprotein B[Invited]Poster presentation
- 10th International Conference on HHV-6&7, Jul. 2017, English, 10th International Conference on HHV-6&7, ベルリン, ドイツ, International conferenceHHV-6 infection and the cellular receptorNominated symposium
- 10th International Conference on HHV-6&7, Jul. 2017, English, 10th International Conference on HHV-6&7, ベルリン, ドイツ, International conferenceExpression of CD134(OX40) on T cells is a trigger of human herpesvirus 6B reactivation and replication after hematopoietic cell transplantation[Invited]Poster presentation
- 10th International Conference on HHV-6&7, Jul. 2017, English, 10th International Conference on HHV-6&7, ベルリン, ドイツ, International conferenceCoexpression of HHV-6B gH/gL/gQ1/gQ2 complex with gB induces cell-cell fusion in CD134 expression cells, and gQ1 and gQ2 are key players for their mediated-cell fusion[Invited]Oral presentation
- 第31回ヘルペスウイルス研究会, Jun. 2017, Japanese, 第31回ヘルペスウイルス研究会, 松江, Domestic conference造血幹細胞移植後のT細胞におけるCD134(OX40）の発現が、移植後HHV-6B再活性化および増殖の誘因となるOral presentation
- 第31回ヘルペスウイルス研究会, Jun. 2017, Japanese, 第31回ヘルペスウイルス研究会, 松江, Domestic conferenceヘルペスウイルスが持つ宿主ユビキチンリガーゼ制御分子の横断的解析Oral presentation
- 第31回ヘルペスウイルス研究会, Jun. 2017, Japanese, 第31回ヘルペスウイルス研究会, 松江, Domestic conferenceヒトヘルペスウイルス 6Bの免疫誘導についての解析Oral presentation
- 第31回ヘルペスウイルス研究会, Jun. 2017, Japanese, 第31回ヘルペスウイルス研究会, 松江, Domestic conferenceヒトヘルペスウイルス6A 転写活性化因子 IE2 C 末端領域の立体構造解析Oral presentation
- 第31回ヘルペスウイルス研究会, Jun. 2017, Japanese, 第31回ヘルペスウイルス研究会, 松江, Domestic conferenceHHV-6B糖タンパク質によって引き起こされる宿主細胞膜融合の解析Oral presentation
- 第31回ヘルペスウイルス研究会, Jun. 2017, Japanese, 第31回ヘルペスウイルス研究会, 松江, Domestic conferenceFunctional analysis of the human herpesvirus 6 envelope glycoprotein BOral presentation
- 神戸大学先端融合研究環新規プロジェクトキックオフシンポジウム－神戸オリジナルをめざして－, May 2017, English, 神戸大学先端融合研究環新規プロジェクトキックオフシンポジウム, 神戸, Domestic conference感染症国際共同研究拠点Nominated symposium
- 第2回Ocular Surface & Glaucoma Seminar, May 2017, Japanese, Ocular Surface & Glaucoma Seminar, 千代田区(東京都), Domestic conferenceヘルペスウイルス感染症[Invited]Invited oral presentation
- 第64回日本ウイルス学会学術集会, Nov. 2016, English, 札幌, Domestic conferenceSeroevidence for high prevalence of infections with avian influenza A(H5N1) virus among workers in a live poultry market in Indonesia.Oral presentation
- 12nd Congress for Asian Society for Pediatric Research 2016, Nov. 2016, English, Congress for Asian Society for Pediatric Research, Bangkok, Thailand, International conferenceComprehensive analysis of serum cytokines/chemokines in febrile children with primary human herpes virus-6B infectionPoster presentation
- The 64th Annual Meeting of the JapaneseSociety for Virology, Oct. 2016, Japanese, 日本ウイルス学会, 札幌, Domestic conferenceNewly identification and functional analysis of host molecules building to HHV-6Oral presentation
- The 64th Annual Meeting of the JapaneseSociety for Virology, Oct. 2016, Japanese, 日本ウイルス学会, 札幌, Domestic conferenceSeroevidence for high prevalence of infections with avian influenza A(H5N1) virus among workers in a live poultry market in IndonesiaOral presentation
- The 64th Annual Meeting of the JapaneseSociety for Virology, Oct. 2016, Japanese, 日本ウイルス学会, 札幌, Domestic conferenceThe role of U14 in human herpesvirus-6 infection[Invited]Oral presentation
- The 64th Annual Meeting of the JapaneseSociety for Virology, Oct. 2016, Japanese, 日本ウイルス学会, 札幌, Domestic conferenceStructual insight into the function of human herpesvirus-6B tegument protein U14[Invited]Oral presentation
- 41st Annual International Herpesvirus Workshop, Jul. 2016, English, 41st Annual International Herpesvirus Workshop, Madison, USA, International conferenceThe cellilar Prolyl cis/trans Isomerase Pin1 Promotes the Disassembly of the Nuclear LaminaPoster presentation
- 41st Annual International Herpesvirus Workshop, Jul. 2016, English, 41st Annual International Herpesvirus Workshop, Madison, USA, International conferenceRe-Assessment of the Role of the ORF0 Stop-Codon Mutation in Herpes Zoster Caused by the Varicella Vaccine Strain vOkaOral presentation
- 41st Annual International Herpesvirus Workshop, Jul. 2016, English, 41st Annual International Herpesvirus Workshop, Madison, USA, International conferenceIdentification of the Cellular Factor which Interacts with HHV-6B U14Oral presentation
- 41st Annual International Herpesvirus Workshop, Jul. 2016, English, 41st Annual International Herpesvirus Workshop, Madison, USA, International conferenceEntry Mechanism of Human Herpesvirus 6A/B into Cells[Invited]Nominated symposium
- 第19回日本ワクチン学会学術集会, Nov. 2015, Japanese, 尾崎 隆男, 愛知, Domestic conferenceヒトヘルペスウイルス6Bワクチン開発の試み[Invited]Oral presentation
- 9th INTERNATIONAL CONFERENCE ON HHV-6 & 7, Nov. 2015, English, Louis Flamand,Philip E. Pellett, Boston, アメリカ, International conferenceThe role of Cytoplasmic Tail of CD134 in HHV-6B Infection[Invited]Poster presentation
- 9th International Conference on HHV-6&7, Nov. 2015, English, HHV-6 FOUNDATION, Boston, アメリカ, International conferenceSerum levels of cytokines/chemokines during primary infection of HHV-6B.[Invited]Oral presentation
- 第63回日本ウイルス学会学術集会, Nov. 2015, English, 柳 雄介, 福岡, Domestic conferenceIsolation of avian H3N6 influenza virus from a poultry duck at a wet market in East Java鳥H3N6インフルエンザウイルスの家禽からの分離[Invited]Poster presentation
- 9th INTERNATIONAL CONFERENCE ON HHV-6 & 7, Nov. 2015, English, Louis Flamand,Philip E. Pellett, Boston, アメリカ, International conferenceIdentification of Cellurar Factor Interesting with Human Hervesvirus-6 U14[Invited]Oral presentation
- 第63回日本ウイルス学会学術集会, Nov. 2015, Japanese, 柳 雄介, 福岡, Domestic conferenceIdentification of cellurar factor Interected with human hervesvirus-6 U14[Invited]Oral presentation
- 第63回日本ウイルス学会学術集会, Nov. 2015, Japanese, 柳 雄介, 福岡, Domestic conferenceHuman Herpesvirus-6 U14induces cell-cycle arrest inG2/M phase[Invited]Oral presentation
- 第63回日本ウイルス学会学術集会, Nov. 2015, Japanese, 柳 雄介, 福岡, Domestic conferenceHuman Herpesvirus-6 U11 is critical for virus infection[Invited]Oral presentation
- 第63回日本ウイルス学会学術集会, Nov. 2015, English, 柳 雄介, 福岡, Domestic conferenceFunctional Analysis of the cytoplasmic tail of CD134 during HHV-6B infectionHHV-6B 侵入におけるCD134分子の細胞質側領域の機能解析[Invited]Poster presentation
- 第63回日本ウイルス学会学術集会, Nov. 2015, English, 日本ウイルス学会, 福岡, Domestic conferenceFunctional analysis of the cytoplasmic tail of CD134 during HHV-6B infection.[Invited]Poster presentation
- 第63回日本ウイルス学会学術集会, Nov. 2015, Japanese, 柳 雄介, 福岡, Domestic conferenceFunctional analysis of sialic acids on varicella-zoster virus glycoprotein B水痘帯状疱疹ｳｲﾙｽｸﾞﾘｺﾌﾟﾛﾃｲﾝB上のｼｱﾙ酸の機能解析Oral presentation
- 9th INTERNATIONAL CONFERENCE ON HHV-6 & 7, Nov. 2015, English, Louis Flamand,Philip E. Pellett, Boston, アメリカ, International conferenceConstruction of Human Herpesvirus-6 Recombinant Virus and its AspplicationInvited oral presentation
- 第63回日本ウイルス学会学術集会, Nov. 2015, English, 柳 雄介, 福岡, Domestic conferenceCo-infection of avian and seasonal influenza viruses among workers at wet market in East Java鳥及び季節性インフルエンザの重感染Oral presentation
- 第63回日本ウイルス学会学術集会, Nov. 2015, English, 柳 雄介, 福岡, Domestic conferenceAnalysis of humoral immunity in guinea pigs immunized with recombinant varicella vaccine viruses.Poster presentation
- 9th INTERNATIONAL CONFERENCE ON HHV-6 & 7, Nov. 2015, English, Louis Flamand,Philip E. Pellett, Boston, アメリカ, International conferenceA gB epitope Important for Neutralizing Antibody Recognition is not Essential for HHV-6A PropagationPoster presentation
- The 14th Aawaji International Forum on Infection and Immunity, Sep. 2015, English, Yasushi Kawaguchi, 兵庫, Domestic conferenceIdentification of amino acid residues within CD134 required for HHV-6B infection[Invited]Oral presentation
- 第29回ヘルペスウイルス研究会, May 2015, Japanese, 峰松俊夫、森内浩幸, 長崎, Domestic conference組換え水痘ワクチンウイルスの免疫誘導に関する検討Oral presentation
- 第29回ヘルペスウイルス研究会, May 2015, Japanese, 峰松俊夫、森内浩幸, 長崎, Domestic conference水痘帯状疱疹ウイルス（VZV)感染における糖鎖機能の解析Oral presentation
- 第29回ヘルペスウイルス研究会, May 2015, Japanese, 峰松俊夫、森内浩幸, 長崎, Domestic conferenceHHV-6Bの侵入におけるCD134分子の細胞質側領域の機能解析[Invited]Oral presentation
- 第29回ヘルペスウイルス研究会, May 2015, Japanese, 峰松俊夫、森内浩幸, 長崎, Domestic conferenceHHV-6A ｇB変異体ウイルスを用いた中和エピトープの解析Oral presentation
- 第29回ヘルペスウイルス研究会, May 2015, Japanese, 峰松俊夫、森内浩幸, 長崎, Domestic conferenceHHV-6A/B U14と相互作用するウイルス因子の同定Oral presentation
- 第89回日本感染症学会学術講演会, Apr. 2015, Japanese, 一山 智, 京都, Domestic conference現行の水痘ワクチンを用いた次世代ワクチンの開発[Invited]Nominated symposium
- 第61回日本ウイルス学会学術集会, Nov. 2013, Japanese, 日本ウイルス学会, 兵庫県神戸市, Domestic conference水痘帯状疱疹ウイルス(VZV)の膜融合メカニズムの解析[Invited]Oral presentation
- 第17回日本ワクチン学会学術集会, Nov. 2013, Japanese, 日本ワクチン学会, 三重県津市, Domestic conference水痘ワクチンウイルスベクター[Invited]Nominated symposium
- 第61回日本ウイルス学会学術集会市民講座, Nov. 2013, Japanese, ヘルペスウイルス研究会, 兵庫県神戸市, Domestic conferenceヘルペスウイルス感染症[Invited]Public discourse
- 京滋ヘルペス感染症研究会, Nov. 2013, Japanese, グラクソ・スミスクライン, 京都府京都市, Domestic conferenceヒトヘルペスウイルス6の感染機構[Invited]Invited oral presentation
- 第61回日本ウイルス学会学術集会, Nov. 2013, Japanese, 日本ウイルス学会, 兵庫県神戸市, Domestic conferenceヒトヘルペスウイルス6B感染により引き起こされる宿主因子の発現低下[Invited]Oral presentation
- 第61回日本ウイルス学会学術集会, Nov. 2013, Japanese, 日本ウイルス学会, 兵庫県神戸市, Domestic conferenceヒトヘルペスウイルス6A/Bの宿主細胞への侵入機構に関する研究[Invited]Nominated symposium
- 第17回日本ワクチン学会学術集会, Nov. 2013, Japanese, 日本ワクチン学会, 三重県津市, Domestic conferenceRSウイルスのF抗原を発現する組換え水痘ワクチンの作製とその有効性の検討[Invited]Oral presentation
- 第61回日本ウイルス学会学術集会, Nov. 2013, English, 日本ウイルス学会, 兵庫県神戸市, Domestic conferenceNA subype impact on Influenza intranasal inactivated whole virion vaccine[Invited]Oral presentation
- 第17回日本ワクチン学会学術集会, Nov. 2013, Japanese, 日本ワクチン学会, 三重県津市, Domestic conferenceMHC class I分子はHHV-6ウイルス粒子に乗って細胞外へ放出される[Invited]Poster presentation
- 第61回日本ウイルス学会学術集会, Nov. 2013, English, 日本ウイルス学会, 兵庫県神戸市, Domestic conferenceHuman herpesvirus 6 U21 to U24 gene cluster is not essential for the virus growth[Invited]Oral presentation
- 第61回日本ウイルス学会学術集会, Nov. 2013, Japanese, 日本ウイルス学会, 兵庫県神戸市, Domestic conferenceHCV非構造タンパク質NS3遺伝子を発言する組換え水痘ワクチンの作製[Invited]Poster presentation
- 第61回日本ウイルス学会学術集会, Nov. 2013, Japanese, 日本ウイルス学会, 神戸, Domestic conferenceHCV非構造タンパク質NS3遺伝子を発現する組換え水痘ワクチンウイルスの作製[Invited]Oral presentation
- 第61回日本ウイルス学会学術集会, Nov. 2013, English, 日本ウイルス学会, 兵庫県神戸市, Domestic conferenceFunctional analysis of human herpesvirus 6B entry receptor and its viral ligand[Invited]Oral presentation
- 第61回日本ウイルス学会学術集会, Nov. 2013, Japanese, 日本ウイルス学会, 兵庫県神戸市, Domestic conferenceDextra sulfateによるインフルエンザウイルスNeuraminidase活性阻害の解析[Invited]Oral presentation
- 北海道大学遺伝子制御研究所研究集会, Oct. 2013, Japanese, 北海道大学遺伝子制御研究所, 北海道札幌市, Domestic conferenceヒトヘルペスウイルス6への宿主細胞析へのエントリー機構[Invited]Invited oral presentation
- 第20回ヘルペス感染症フォーラム, Aug. 2013, Japanese, ヘルペス感染症研究会, 北海道札幌市, Domestic conferenceHHV-6A/B研究の進展[Invited]Invited oral presentation
- 38th International Herpes Workshop, Jul. 2013, English, International Herpes Virus Workshop, Grand Rapids, Michigan, USA, International conferenceIdentification of an Entry Receptor Specific for HHV-6B Infection[Invited]Oral presentation
- 38th International Herpes Workshop, Jul. 2013, English, International Herpes Virus Workshop, Grand Rapids, Michigan, USA, International conferenceDevelopment of a Recombinant Varicella Zoster Vaccine Zoster Vaccine Expressing Repiratory Syncytial Virus Fusion[Invited]Oral presentation
- 第28回ヘルペスウイルス研究会, May 2013, Japanese, ヘルペスウイルス研究会, 兵庫県淡路市, 香川県小豆郡帯状疱疹プロジェクトは3年間のコホート研究であり、帯状疱疹と免疫との関係を検討したところ、水痘帯状疱疹ウイルス特異的細胞性免疫が帯状疱疹の発症抑制、帯状疱疹後神経痛および重症化の予防に重要な役割を果たしていることが示唆された。, Domestic conference帯状疱疹の発症リスクおよび重症度と細胞性免疫との相関[Invited]Oral presentation
- 第28回ヘルペスウイルス研究会, May 2013, Japanese, ヘルペスウイルス研究会, 兵庫県淡路市, 水痘帯状疱疹ウイルスglycoproteinH (gH) と免疫グロブリンFcタンパクとの融合タンパクを作製し、その解析を行ったところ、gHと結合する受容体の同定に成功した。, Domestic conference水痘帯状疱疹ウイルス(VZV)glycoprotein H(gH)受容体の解析[Invited]Oral presentation
- 第28回ヘルペスウイルス研究会, May 2013, Japanese, ヘルペスウイルス研究会, 兵庫県淡路市, ヒトヘルペスウイルス6B (HHV-6B) 感染において、その感染特異的に細胞膜表面からの発現低下が認められた、免疫学的シナプスの構成因子であるスカベンジャーレセプターを同定した。, Domestic conferenceヒトヘルペスウイルス6B感染による宿主細胞のシグナルと免疫抑制の解析[Invited]Oral presentation
- 第28回ヘルペスウイルス研究会, May 2013, Japanese, ヘルペスウイルス研究会, 兵庫県淡路市, 水痘ワクチンウイルスゲノムに、RSウイルス (RSV) の表面抗原であるG抗原あるいはF抗原の遺伝子をvOkaに組み込み、GあるいはFを発現させた組換え水痘ウイルスを作製するとともに、これらのウイルスのVZVおよびRSVに対する抗体が誘導できるか否かを検討し、その効果を確認した。, Domestic conferenceRSウイルスの抗原遺伝子を発現する組換え水痘多価ワクチンの作製とその有効性の検討[Invited]Oral presentation
- 第28回ヘルペスウイルス研究会, May 2013, English, ヘルペスウイルス研究会, 兵庫県淡路市, We found the molecule specifically interacting with human herpesvirus-6B (HHV-6B) ligand but not HHV-6A ligand. This molecule could been blocked the HHV-6B infection. And HHV-6B infection could also been inhibited by knocking doen the molecule in HHV-6B permissive cells., Domestic conferenceIdentification of a cellular molecule required for HHV-6B entry[Invited]Oral presentation
- 第28回ヘルペスウイルス研究会, May 2013, English, ヘルペスウイルス研究会, 兵庫県淡路市, Domestic conferenceHuman herpesvirus 6 U21 to U24 genes are not essential for the virus growth[Invited]Oral presentation
- 第28回ヘルペスウイルス研究会, May 2013, Japanese, ヘルペスウイルス研究会, 兵庫県淡路市, Domestic conferenceHHV-6ウイルス粒子に存在する宿主因子の解析[Invited]Oral presentation
- 第28回ヘルペスウイルス研究会, May 2013, Japanese, ヘルペスウイルス研究会, 兵庫県淡路市, ヒトヘルペスウイルス6A (HHV-6A) gQ1に対する中和モノクローナル抗体を得ることに成功し、それを用いた解析を行い、HHV-6A gQ1における中和抗体の認識部位および細胞侵入に重要な領域を明らかにした。, Domestic conferenceHHV-6A gQ1の様々な機能および構造維持に重要な領域の同定[Invited]Oral presentation
- 第28回ヘルペスウイルス研究会, May 2013, Japanese, ヘルペスウイルス研究会, 兵庫県淡路市, 水痘ワクチン株ゲノムに、C型肝炎ウイルスがコードする非構造タンパクであるNS3遺伝子を組み込んだ組換え水痘ワクチンウイルスの作製に成功した。, Domestic conferenceHCV非構造タンパク質NS3遺伝子を発言する組換え水痘ワクチンの作製[Invited]Oral presentation
- 8th International Confernece on HHV-6 & 7, Apr. 2013, English, HHV-6 Foundation, Paris, France, International conferencehuman Herpesvirus-6A/B entry into host cells[Invited]Invited oral presentation
- 第60回日本ウイルス学会学術集会, Nov. 2012, Japanese, 日本ウイルス学会, 大阪, 本研究では、水痘帯状疱疹ウイルス（VZV）の宿主細胞への侵入の際、ウイルス側のタンパクであるgBと宿主因子MAGとの結合について詳細な解析を行った。シアリダーゼ処理およびgB発現細胞のN型糖鎖修飾を阻害することによって、gB発現細胞への、MAGの会合・膜融合・VZV感染が阻害された。このことから、gBとMAGの会合には、gB上のN型糖鎖に結合シアル酸が必須であることが判明した。, Domestic conference水痘帯状疱疹ウイルス（VZV）の感染におけるシアル酸の役割[Invited]Oral presentation
- 第60回日本ウイルス学会学術集会, Nov. 2012, Japanese, 日本ウイルス学会, 大阪, 本研究では、水痘帯状疱疹ウイルス（VZV）特異的CMIを誘導するVZVタンパクの探索を行った。水痘既往のある健常人の末梢血単核球を材料とし、Elispot法を用いて、13種類のウイルスタンパク抗原について調べた結果、ORF4、61、62、63、66の5種類のタンパクに対する反応が高頻度に検出された。特に、トランス転写抑制因子をコードするORF63に対する特異的CMI応答は全被検者に認められた。, Domestic conference水痘帯状疱疹ウイルス特異的細胞性免疫を誘導する抗原の探索[Invited]Oral presentation
- 第60回日本ウイルス学会学術集会, Nov. 2012, Japanese, 日本ウイルス学会, 大阪, 水痘帯状疱疹ウイルス(varicella-zoster virus : VZV)はαヘルペスウイルス亜科に属し、ヒトを唯一の宿主とする。αヘルペスウイルスはmRNA発現調節様式として、βヘルペスウイルスあるいはγヘルペスウイルスに比べ、splicingによる転写後調節はほとんどなく、結果mRNAからのタンパク発現において多様性が少ないと考えられてきた。近年我々は、VZV感染細胞より調整したcDNAを用いることにより、ウイルス粒子糖タンパクであるglycoprotein MをコードするORF50をはじめとする複数の後期遺伝子において、alternative splicingによりそのmRNA発現が制御されていることを明らかにしてきた。さらに現在まで報告のない前初期遺伝子に対する新規anti-sense transcriptを発見し、このtranscri, Domestic conference水痘帯状疱疹ウイルスにおける新規遺伝子産物の発見とその機能解析[Invited]Oral presentation
- 第16回日本ワクチン学会学術集会, Nov. 2012, Japanese, 日本ワクチン学会, 横浜, 水痘予防生ワクチンとして世界中で使用されているのは、水痘ワクチン岡株（vOka）であり、高い有効性と安全性を持つことが実証されている。我々は、このvOka全ゲノムをBAC （bacterial artificial chromosome）に挿入し、さらにこの全ゲノムを水痘ウイルス感受性細胞に導入することでワクチンゲノムからの感染性ウイルスの再構築に成功した。BACは大腸菌内で保持されており、このBACシステムを用いることにより、大腸菌内でvOkaゲノムに変異を導入することが可能となった。そこで、このvOkaゲノムに、他の病原体の抗原遺伝子を挿入した組換え水痘ワクチンを作製し、水痘ウイルスだけでなく他のウイルス感染症も阻止できる多価生ワクチンの開発を試みた。我々は、今回外来遺伝子としてターゲットとしたのはムンプスウイルスの抗原遺伝子である。現行の水痘ワ, Domestic conference水痘ワクチンの組換えワクチンベクターとしての応用[Invited]Oral presentation
- 第16回日本ワクチン学会学術集会, Nov. 2012, Japanese, 日本ワクチン学会, 横浜, インフルエンザワクチンンの経鼻感染は、粘膜表層への抗インフルエンザIgA抗体の産生を誘導し、インフルエンザウイルス感染における交叉防御効果に関与すると考えられている。今回、我々が作製した抗インフルエンザIgAモノクローナル抗体(IgA mAb)による交叉防御のメカニズムについて検討した。IgA mAbのウイルスに対する交叉反応性をELISA法ならびに中和抗体測定法により検討した。また、抗体の単量体部分と多量体部分をゲルクロマトグラフィーにより分離・精製し、其々の分画の中和活性を検討した。作製したIgA mAbは、単量体、1.5量体、2量体、3量体の形態をしていた。また、単量体よりも多量体の方が有意に高い中和活性を示していた。しかし、IgA mAbは異なる亜型に対しては交叉反応を示さなかった。現在、交叉中和反応に関与するアミノ酸部分の検索を行っている。, Domestic conference抗インフルエンザIgAモノクローナル抗体による交叉防御効果の性状解析[Invited]Oral presentation
- 第16回日本ワクチン学会学術集会, Nov. 2012, Japanese, 日本ワクチン学会, 横浜, 水痘ウイルス（VZV）岡ワクチン株（vOka）をベースとし、ムンプスウイルス（MuV）の中和抗体の標的抗原とされる膜タンパク質であるhemagglutinin-neuraminidase(HN)と、Fusion(F)を同時に発現させた組換え水痘ウイルスを作製した。モルモット接種試験により、VZV及びMuVに対する高い免疫誘導が得られたことから、VZVとMuVの両方に効果のある多価生ワクチンとしての有用性が期待できると考えられる。, Domestic conferenceムンプスウイルスの抗原遺伝子を有する組換え水痘ワクチン開発のための応用研究[Invited]Oral presentation
- 第60回日本ウイルス学会学術集会, Nov. 2012, Japanese, 日本ウイルス学会, 大阪, 本研究では、HHV-6の膜融合アッセイを確立し、HHV-6の細胞に侵入の際、必要なウイルスのタンパク（gH、gL、gOとgB）を同定した。また、CD46-Igとの相互作用の解析結果、gB、gOはCD46とウイルスのリガンドであるgH/gL/gQ1/gQ2複合体との相互作用に関係しないことが明らかとなった。また、この融合アッセイはCD46の過剰発現によって促進されることも明らかとなった。, Domestic conferenceヘルペスウイルス6型の膜融合はgB,gH,gL,gQによって引き起こされる[Invited]Oral presentation
- 第60回日本ウイルス学会学術集会, Nov. 2012, Japanese, 日本ウイルス学会, 大阪, ヒトヘルペスウイルス6A (HHV-6A) がコードする糖タンパク、glycoprotein M (gM) /gN複合体と相互作用する宿主因子として既に同定済である、小胞輸送に重要なSNAREタンパクのHHV-6A感染T細胞内における動態の観察を行い、SNAREがその感染に重要な因子である可能性が示唆された。, Domestic conferenceヒトヘルペスウイルス6感染によって引き起こされる宿主変化[Invited]Oral presentation
- 第60回日本ウイルス学会学術集会, Nov. 2012, Japanese, 日本ウイルス学会, 大阪, パンデミックインフルエンザウイルスA型の予測は困難である。そこで、インフルエンザウイルスライブラリーを用いた、新たなワクチン構築を検討している。インフルエンザウイルスライブラリーから、パンデミックウイルスと同じ亜型で、近い抗原性を持つウイルスを用いてワクチンを試作し、接種することで交叉防御免疫を誘導することを計画した。H5N1の株を採取・培養し、このウイルスを精製・不活化し、不活化全粒子ワクチンを作製した。このワクチンをマウスに経鼻接種し、最終接種から2週間後に、ワクチン株と同じHA抗原性を有する株、又は同じ亜型の変異株で最も異なる抗原性を有する株に対する感染防御効果を検討した。結果、同じ亜型(H5N1)の異なるウイルス株の致死感染に対し、全例感染死を免れた。またワクチン株とは異なる亜型(H1N1,H3N2)のウイルス株に対しても感染死をほぼ免れた。, Domestic conferenceパンデミックインフルエンザの発生に即応した、ワクチン製造用種ウイルス株の作出—インフルエンザウイルスライブラリーの利用—[Invited]Oral presentation
- 第16回日本ワクチン学会学術集会, Nov. 2012, Japanese, 日本ワクチン学会, 横浜, 新たに発生するA型インフルエンザの型の予測は困難である。そこで、インフルエンザウイルスライブラリーを用いたパンデミックに即応し得る、新たなワクチン構築を検討している。インフルエンザウイルスライブラリーからA/duck/Hokkaido/Vac-03/07株(H5N1)を採取・培養し、このウイルスを精製・不活化し、不活化全粒子ワクチンを作製した。このワクチンをマウスに経鼻接種し、最終接種から2週間後に、ワクチン株と同じHA抗原性を有する株、又は同じ亜型の変異株で最も異なる抗原性を有する株に対する感染防御効果を検討した。結果、同じ亜型(H5N1)の異なるウイルス株の致死感染に対し、全例感染死を免れた。またワクチン株とは異なる亜型(H1N1,H3N2)のウイルス株に対しても感染死をほぼ免れた。以上の結果は、インフルエンザウイルスライブラリーを利用した不活化, Domestic conferenceインフルエンザウイルスライブラリーを利用した、パンデミックインフルエンザに即応し得る新規ワクチンの検討[Invited]Oral presentation
- 第60回日本ウイルス学会学術集会, Nov. 2012, Japanese, 日本ウイルス学会, 大阪, Glycoprotein O (gO) is abundantly expressed in HHV-6A virion, however little is known about this protein. To analyze HHV-6A gO maturation process, we used transient expression system in 293T cells and found gO's maturation was accompanied with the deletion of its C-terminal, and that gH and gL were required for its maturation. We also constructed gO-deleted virus and found, Domestic conferencegO is dispensable gene for HHV-6A growth in T cell[Invited]Oral presentation
- 第60回日本ウイルス学会学術集会, Nov. 2012, Japanese, 日本ウイルス学会, 大阪, 近年インフルエンザウイルスNAを標的とした各種薬剤に対する耐性株が広く検出され、異なるメカニズムに基づく抗ウイルス薬の開発が望まれている。今回、Dextran Sulfate(DS)が、インフルエンザウイルスの感染を阻害することに着目し、メカニズムを解析した。さまざまな亜型の株(PR8、Panama、WSN、Brisbane、NY株)をMDCK細胞に感染させ、感染を通じて、もしくはウイルス増殖前期ないし後期のみにDSを添加し、ウイルス増殖能の変化を検討した。さらにDSによるウイルスのNA活性の変化も検討した。DSにより、PR8、Panama株ではウイルス増殖が阻害されたが、WSN、Brisbane、NY株では有意な阻害は見られなかった。DS添加により、PR8、Panama株のNA活性が強く阻害されるとともに、ウイルス粒子の細胞膜からの放出も阻害されて, Domestic conferenceDextran sulfateによるインフルエンザウイルス増殖の阻害とNA活性抑制との関連性[Invited]Oral presentation
- 第60回日本ウイルス学会学術集会, Nov. 2012, Japanese, 日本ウイルス学会, 大阪, Influenza vaccines effectively prevent influenza virus infections. Several reports demonstrated that mucosal immunization, but not subcutaneous immunization, induced cross-protection, suggesting that mucosal IgA might be responsible for this cross-protection. Although IgA is the major contributor to humoral mucosal immunity, there is no direct evidence proving that anti-influen, Domestic conferenceCross-neutralization activity of anti-influenza IgA monoclonal antibody[Invited]Oral presentation
- 37th International Herpesvirus Workshop, Aug. 2012, English, International Herpesvirus Workshop, Calgary,US, Human herpesvirus-6 is T lymphotropic herpesvirus and can be classified into variant A and B (HHV-6A and HHV-6B) by their distinct sequences and pathogenicity. Previously, we have reported that HHV-6A glycoprotein Q1(AgQ1) forms a complex with gQ2, gH and gL and this complex binds to CD46, cellular receptor for HHV-6A. We produced a neutralizing monoclonal antibody (Mab) named, International conferenceIdentification of HHV-6 gQ1 domain which is essential for functional conformation[Invited]Poster presentation
- 37th International Herpesvirus Workshop, Aug. 2012, English, International Herpesvirus Workshop, Calgary,US, In this study, we tried to identify key molecules in gH/gL/gQ1/gQ2 complex, the ligand of HHV-6A for its cellular receptor, CD46, by replacing the components of the complex with corresponding molecules in HHV-6B. We found each molecule, gH, gL, gQ1 or gQ2 of HHV-6B could complement each function of HHV-6A for the complex formation. However, HHV-6A complex expressing HHV-6B gQ1, International conferenceHHV-6 gQ1 is key factor for determination of the variant specific cell tropism[Invited]Oral presentation
- 37th International Herpesvirus Workshop, Aug. 2012, English, International Herpesvirus Workshop, Calgary,US, We tried to identify the different function of gH between HHV-6 variants. We substituted HHV-6A gH with HHV-6B gH in HHV-6A genome. Then, we compared the reconstituted chimera virus with reconstituted wild virus. We found that HHV-6B gH could functionally work during HHV-6A infection with slightly defected growth, that an HHV-6B specific neutralizing antibody could block the e, International conferenceFunctional analysis of HHV-6 gH in an infection context[Invited]Poster presentation
- 第27回ヘルペスウイルス研究会, Jun. 2012, Japanese, ヘルペスウイルス研究会, 愛知県知多郡, VZVのglycoprotein Bと結合する神経組織特異的なMyelin-associated glycoprotein(MAG)が、レセプターとしてVZVの神経組織への侵入にする際に重要であると報告した。このレセプターとリガンドにおけるシアル酸の関与を明らかにした。MAG又はgB発現細胞などを用い、酵素処理(シアル酸除去)、薬剤処理（糖鎖修飾阻害）、MAG・gBへの変異導入を行い、MAGを介した膜融合。感染を解析した。gBとMAGとの会合には、gB上のN、O型糖鎖に結合したシアル酸が重要であり、逆に細胞上のシアル酸はgBとMAGとの会合を阻害していた。, Domestic conference水痘帯状疱疹ウイルス（VZV）の膜融合におけるシアル酸の役割[Invited]Oral presentation
- 第27回ヘルペスウイルス研究会, Jun. 2012, Japanese, ヘルペスウイルス研究会, 愛知県知多郡, 水痘帯状疱疹ウイルス(varicella-zoster virus : VZV)ORF49遺伝子は広くヘルペスウイルスに保存されるコア遺伝子であり、その遺伝子産物ORF49タンパクは、VZV感受性細胞であるMRC-5細胞においては完全に非必須である。しかし、同じくVZV感受性細胞であり、VZV感染拡大においてより完全なウイルス粒子産生を必要とするMeWo細胞においては、その充分な感染拡大に必要であり、VZV感染において報告されている数少ない細胞向性因子の一つである事を我々は報告した。またこれまでに本研究会においてi)ORF49タンパクが、ORF44遺伝子産物（ORF44タンパク）と相互作用すること、ii)この相互作用に機能するアミノ酸をORF49タンパクおよびORF44タンパクにおいて同定し、iii)ORF44タンパクのORF49タンパクとの相互作用, Domestic conference水痘帯状疱疹ウイルスORF49はORF44との相互作用を通して、感染性ウイルス粒子産生に 機能する[Invited]Oral presentation
- 第27回ヘルペスウイルス研究会, Jun. 2012, Japanese, ヘルペスウイルス研究会, 愛知県知多郡, 水痘ウイルス(VZV)岡ワクチン株（vOka）をベースとし、ムンプスウイルス（MuV）のhemagglutinin-neuraminidase(HN)を発現させた組換え水痘ウイルスを作製した。さらに、MuVのもうひとつの膜タンパク質であり、中和抗体の標的抗原であるFusion(F)を発現させた組換え水痘ワクチンウイルスを作製した。モルモット接種試験により、VZVとMuVに対して中和活性、細胞間抑制効果を示したことから、Fも免疫応答に寄与していることが示唆された。, Domestic conferenceムンプスウイルスの抗原遺伝子を発現する水痘ワクチンウイルスの作製とその有効性の検討[Invited]Oral presentation
- 第27回ヘルペスウイルス研究会, Jun. 2012, Japanese, ヘルペスウイルス研究会, 愛知県知多郡, ヒトヘルペスウイルス6 (HHV-6) がコードする糖タンパク、glycoprotein M (gM) /gN複合体と相互作用する宿主因子として、小胞輸送に重要なSNAREタンパクの同定に成功し、HHV-6A感染T細胞においてその詳細な解析を行った結果、この相互作用がHHV-6Aの感染に重要であることを見出した。, Domestic conferenceヒトヘルペスウイルス 6 gM/gN複合体と相互作用する宿主因子に関する解析[Invited]Oral presentation
- 第27回ヘルペスウイルス研究会, Jun. 2012, Japanese, ヘルペスウイルス研究会, 愛知県知多郡, A live attenuated varicella vaccine, the Oka strain (vOka), was developed originally by Takahashi et al. in Japan. Currently, it is used worldwide for immunization of children against varicella. In an attempt to develop vOka as an effective polyvalent vaccine vector, we have sought for promoters that are suitable for expressing foreign genes. We previously reported that HHV-6 m, Domestic conferencePromoter activity of the varicella-zoster virus glycoprotein E[Invited]Oral presentation
- 第27回ヘルペスウイルス研究会, Jun. 2012, Japanese, ヘルペスウイルス研究会, 愛知県知多郡, HHV-6がコードするU14遺伝子は、ウイルス感染初期に発現し、テグメントタンパクとしてウイルス粒子中に取り込まれる。ウイルス感染におけるU14遺伝子の機能を解析することを目的として、U14遺伝子欠損ウイルスの作製を試みた。その結果、HHV6-A U14△1285-1800 ゲノムからの感染性ウイルスの再構築は認められなかった。このことから、U14遺伝子はHHV-6の増殖に必要不可欠であることが示唆された。, Domestic conferenceHHV-6 U14 遺伝子の解析[Invited]Oral presentation
- 第27回ヘルペスウイルス研究会, Jun. 2012, Japanese, ヘルペスウイルス研究会, 愛知県知多郡, Glycoprotein O (gO) is conserved in beta-herpesvirus subfamily. The function and maturation of gO during HHV-6A infection were unknown so far. Two forms of gO exist in HHV-6A infected cells, only the small one is incorporated into HHV-6 virions. By anlyzing the maturation process of gO, we found gO's maturation was accompanied with the deletion of its C-terminal, and that, Domestic conferenceAnalyses of the maturation process and function of HHV-6 gO[Invited]Oral presentation
- 7th International Conference on HHV-6 & 7, Mar. 2011, English, HHV-6 foundation, Reston, アメリカ合衆国, International conferenceHHV-6 Glycoprotein Complex Formation is Required for the Folding and Trafficking of the Complex, gH/gL/gQ1/ gQ2 and its Cellular Receptor Binding; gQ1[Invited]Invited oral presentation
- 7th International Conference on HHV-6 & 7, Feb. 2011, English, HHV-6 foundation, Reston, アメリカ合衆国, International conferenceThe Functional Analysis Of Glycoprotein O During HHV-6 Infection: HHV-6 gO is Non- Essential for the Virus Growth in CBMCs[Invited]Oral presentation
- 7th International Conference on HHV-6 & 7, Feb. 2011, English, HHV-6 foundation, Reston, アメリカ合衆国, International conferenceIdentification of the Epitopes on Neutralizing MAb for Human Herpesvirus 6 Glucoprotein Q1[Invited]Oral presentation
- 第14回日本ワクチン学会学術集会, Dec. 2010, Japanese, 日本ワクチン学会, 東京都千代田区, Domestic conference風疹ウイルス構造タンパクを発現する組換え水痘ワクチンの作製[Invited]Oral presentation
- 第14回日本ワクチン学会学術集会, Dec. 2010, Japanese, 日本ワクチン学会, 東京都千代田区, Domestic conference細胞融合を抑制したムンプスウイルスhemagglutinin-neuraminidase及びfusion protein 発現組換え水痘ワクチンの開発[Invited]Oral presentation
- Cell Symposia: Influenza - Translating basic insights, Dec. 2010, English, Elsevier(Cell Press), Washington DC, アメリカ合衆国, International conferenceProtective immune response by intranasal immunization with split-virion influenza A vaccine with adjuvant and whole-viron influenza A vaccine[Invited]Oral presentation
- 第58回日本ウイルス学会学術集会, Nov. 2010, Japanese, 日本ウイルス学会, 徳島市, Domestic conference水痘帯状疱疹ウイルスORF44とORF49における詳細な相互作用解析[Invited]Poster presentation
- 第58回日本ウイルス学会学術集会, Nov. 2010, Japanese, 日本ウイルス学会, 徳島市, Domestic conferenceヒトヘルペスウイルス6 glycoprotein Q1に対する中和抗体の作製とその解析[Invited]Oral presentation
- 第58回日本ウイルス学会学術集会, Nov. 2010, Japanese, 日本ウイルス学会, 徳島市, Domestic conferenceヒトヘルペスウイルス6(HHV-6)がコードするテグメントタンパクU14と細胞周期の関連性[Invited]Poster presentation
- 第58回日本ウイルス学会学術集会, Nov. 2010, Japanese, 日本ウイルス学会, 徳島市, Domestic conferenceHuman herpesvirus-6 encoded glycoprotein Q1 gene is essential for virus growth.[Invited]Poster presentation
- 第47回日本眼感染症学会, Jul. 2010, Japanese, 日本眼感染症学会, 東京, Domestic conference水痘帯状疱疹ウイルス特異的細胞性免疫応答と病態発症[Invited]Invited oral presentation
- 35th International Herpesvirus Workshop, Jul. 2010, English, International Herpesvirus Workshop, Salt Lake City, アメリカ合衆国, International conferenceThe correlation of VZV specific T cell-mediated immunity and the incidence of herpes zoster.[Invited]Poster presentation
- 35th International Herpesvirus Workshop, Jul. 2010, English, International Herpesvirus Workshop, Salt Lake City, アメリカ合衆国, International conferenceMyelin-Associated Glycoprotein Associates with gB and is Involved in Membrane Fusion during Neurotropic Herpesvirus Infection[Invited]Oral presentation
- 35th International Herpesvirus Workshop, Jul. 2010, English, International Herpesvirus Workshop, Salt Lake City, アメリカ合衆国, International conferenceHuman herpesvirus-6 major immediate early promoter functions strongly in T cells and is useful for the various gene expressions.[Invited]Poster presentation
- 35th International Herpesvirus Workshop, Jul. 2010, English, International Herpesvirus Workshop, Salt Lake City, アメリカ合衆国, International conferenceHHV-6 glycoprotein complex formation is required for the folding and trafficking of the complex, gH/gL/gQ1/ gQ2 and its cellular receptor binding[Invited]Oral presentation
- 第25回ヘルペスウイルス研究会, May 2010, Japanese, ヘルペスウイルス研究会, 浜松, Domestic conference膠原病患者における帯状疱疹発症リスクの解析:ELISPOTアッセイによる特異的細胞性免疫能の評価[Invited]Oral presentation
- 第25回ヘルペスウイルス研究会, May 2010, Japanese, ヘルペスウイルス研究会, 浜松, Domestic conference風疹ウイルス構造タンパク発現組換え水痘帯状疱疹ウイルスの作製[Invited]Oral presentation
- 第25回ヘルペスウイルス研究会, May 2010, Japanese, ヘルペスウイルス研究会, 浜松, Domestic conference水痘帯状疱疹ウイルスORF44の解析[Invited]Oral presentation
- 第25回ヘルペスウイルス研究会, May 2010, Japanese, ヘルペスウイルス研究会, 浜松, Domestic conferenceヘルペスウイルス感染における神経組織指向性レセプター[Invited]Oral presentation
- 第25回ヘルペスウイルス研究会, May 2010, Japanese, ヘルペスウイルス研究会, 浜松, Domestic conferenceヒトヘルペスウイルス6前初期プロモーターの解析と組換え水痘ワクチンへの利用[Invited]Oral presentation
- 第25回ヘルペスウイルス研究会, May 2010, Japanese, ヘルペスウイルス研究会, 浜松, Domestic conferenceヒトヘルペスウイルス6がコードする糖タンパク複合体gH/gL/gQ1/gQ2の解析[Invited]Oral presentation
- 第25回ヘルペスウイルス研究会, May 2010, Japanese, ヘルペスウイルス研究会, 浜松, Domestic conferenceヒトヘルペスウイルス6がコードする糖タンパクglycoproteinQ(gQ)に対するモノクローナル抗体作製[Invited]Oral presentation
- 第25回ヘルペスウイルス研究会, May 2010, Japanese, ヘルペスウイルス研究会, 浜松, Domestic conferenceヒトヘルペスウイルス6 glycoprotein Mと相互作用する宿主因子の解析[Invited]Oral presentation
- The 6th Anniversary International Symposium of Bio-MAX Institute, May 2010, English, International Symposium of Bio-MAX Institute, ソウル, 韓国, International conferenceNovel vaccine development based on current varicella vaccine[Invited]Invited oral presentation
- 文部科学省知的クラスター創成事業（第II期）関西広域バイオメディカルクラスター成果発表会, Feb. 2010, Japanese, 文部科学省知的クラスター創成事業, 神戸, Domestic conference水痘ワクチンをベクターとした新世代多価生ワクチンの開発，再生医療・創薬新しい医療の確立を目指して[Invited]Oral presentation
- 第57回日本ウイルス学会学術集会, Oct. 2009, Japanese, 日本ウイルス学会, 東京, Domestic conference水痘帯状疱疹ウイルスワクチン株ORF0は糖タンパク質である[Invited]Oral presentation
- 第57回日本ウイルス学会学術集会, Oct. 2009, Japanese, 日本ウイルス学会, 東京, Domestic conference水痘帯状疱疹ウイルスglycoprotein M の成熟機構の解析[Invited]Oral presentation
- 第57回日本ウイルス学会学術集会, Oct. 2009, Japanese, 日本ウイルス学会, 東京, Domestic conferenceヒトヘルペスウイルス6特異的エンベロープ糖タンパクをコードするgQ遺伝子の解析[Invited]Oral presentation
- 第57回日本ウイルス学会学術集会, Oct. 2009, Japanese, 日本ウイルス学会, 東京, Domestic conferenceヒトヘルペスウイルス6前初期プロモーターの同定と新規外来遺伝子発現用プロモーターとしての応用[Invited]Poster presentation
- 第57回日本ウイルス学会学術集会, Oct. 2009, Japanese, 日本ウイルス学会, 東京, Domestic conferenceヒトヘルペスウイルス6 glycoprotein Mと相互作用する宿主因子の同定および解析[Invited]Oral presentation
- The 14th International Conference on Immunobiology and Prophylaxis of Human Herpesvirus Infections, Oct. 2009, English, International Conference on Immunobiology and Prophylaxis of Human Herpesvirus Infections, 神戸, International conferenceVZV glycoprotein M and glycoprotein N assist each other for their functions.[Invited]Poster presentation
- The 14th International Conference on Immunobiology and Prophylaxis of Human Herpesvirus Infections, Oct. 2009, English, International Conference on Immunobiology and Prophylaxis of Human Herpesvirus Infections, 神戸, International conferenceVaricella zoster virus-specific immunity in patients with diabetes mellitus.[Invited]Poster presentation
- The 14th International Conference on Immunobiology and Prophylaxis of Human Herpesvirus Infections, Oct. 2009, English, International Conference on Immunobiology and Prophylaxis of Human Herpesvirus Infections, 神戸, International conferenceThe ORF0 protein of varicella zoster virus vaccine strain is N-glycosylated.[Invited]Poster presentation
- Japan-France Vaccine and Infectious Diseases Workshop in Osaka, Oct. 2009, English, Japan-France Vaccine and Infectious Diseases Workshop, 大阪, International conferenceNovel polyvalent live vaccine development based on current live varicella vaccine[Invited]Invited oral presentation
- The 14th International Conference on Immunobiology and Prophylaxis of Human Herpesvirus Infections, Oct. 2009, English, International Conference on Immunobiology and Prophylaxis of Human Herpesvirus Infections, 神戸, International conferenceHuman herpesvirus-6 gH/gL/gQ complex and its receptor usage[Invited]Invited oral presentation
- The 14th International Conference on Immunobiology and Prophylaxis of Human Herpesvirus Infections, Oct. 2009, English, International Conference on Immunobiology and Prophylaxis of Human Herpesvirus Infections, 神戸, International conferenceAnalysis of human herpesvirus 6 glycoprotein M.[Invited]Poster presentation
- 第13回日本ワクチン学会学術集会, Sep. 2009, Japanese, 日本ワクチン学会, 北海道, Domestic conference新規ワクチン開発のための水痘ワクチン株のクローン化とその性状解析[Invited]Oral presentation
- The 9th Awaji International Forum on Infection and Immunity, Sep. 2009, English, Awaji International Forum on Infection and Immunity, 淡路島, International conferenceIdentification of human herpes virus 6 major immediate early promoter and application to drive foreign genes.[Invited]Poster presentation
- 第13回日本ワクチン学会学術集会, Sep. 2009, Japanese, 日本ワクチン学会, 北海道, Domestic conferenceConstruction of a recombinant varicella vaccine expressing mumps virus hemagglutinin-neuraminidase and measles virus hemagglutinin proteins[Invited]Oral presentation
- 第24回ヘルペスウイルス研究会, Jul. 2009, Japanese, ヘルペスウイルス研究会, 静岡, Domestic conference糖尿病患者における水痘帯状疱疹ウイルス特異的な免疫応答の抑制の可能性に関する検討[Invited]Oral presentation
- 第24回ヘルペスウイルス研究会, Jul. 2009, Japanese, ヘルペスウイルス研究会, 静岡, Domestic conference水痘帯状疱疹ウイルス ORF0 タンパク質の野生株とワクチン株間における比較[Invited]Oral presentation
- 第24回ヘルペスウイルス研究会, Jul. 2009, Japanese, ヘルペスウイルス研究会, 静岡, Domestic conference水痘帯状疱疹ウイルスglycoprotein Mの詳細な解析[Invited]Oral presentation
- 第24回ヘルペスウイルス研究会, Jul. 2009, Japanese, ヘルペスウイルス研究会, 静岡, Domestic conferenceヒトヘルペスウイルス6 glycoprotein Mと相互作用する宿主タンパク質の同定[Invited]Oral presentation
- 34th International Herpesvirus Workshop, Jul. 2009, English, International Herpesvirus Workshop, イサカ, アメリカ, International conferenceRapid and efficient induction of a foreign gene into BAC-cloned varicella vaccine by transposon Tn7-mediated site-specific transposition.[Invited]Poster presentation
- 34th International Herpesvirus Workshop, Jul. 2009, English, International Herpesvirus Workshop, イサカ, アメリカ, International conferenceNewly identified mRNA arisen from VZV ORF50 gene region was not essential for viral growth.[Invited]Poster presentation
- 34th International Herpesvirus Workshop, Jul. 2009, English, International Herpesvirus Workshop, イサカ, アメリカ, International conferenceHuman herpesvirus 6 envelope components enriched in lipid rafts: evidence for virion-associated lipid rafts.[Invited]Poster presentation
- 第24回ヘルペスウイルス研究会, Jul. 2009, Japanese, ヘルペスウイルス研究会, 静岡, Domestic conferenceGeneration of a transpose-recombinant varicella viral vector: a rapid and efficient genetic manipulation for insertion of a foreign gene by site-specific transposition of the transposon Tn7[Invited]Oral presentation
- 34th International Herpesvirus Workshop, Jul. 2009, English, International Herpesvirus Workshop, イサカ, アメリカ, International conferenceDecreased varicella zoster virus-specific cell-mediated immunity in patients with diabetes mellitus.[Invited]Oral presentation
- 34th International Herpesvirus Workshop, Jul. 2009, English, International Herpesvirus Workshop, イサカ, アメリカ, International conferenceComparison and characterization of VZV encoded ORF0 of the parental and vaccine strains.[Invited]Poster presentation
- 近畿ヘルペス感染症研究会学術講演会, Jun. 2009, Japanese, 近畿ヘルペス感染症研究会, 大阪, Domestic conference帯状疱疹ワクチンについて～帯状疱疹治療未来への展望～[Invited]Invited oral presentation
- 第12回日本ワクチン学会学術集会, Nov. 2008, Japanese, 日本ワクチン学会, 熊本, Domestic conferenceポリ-γ-グルタミン酸ナノ粒子(γ-PGA-NPs)とインフルエンザ-ヘマグルチニンワクチンとの併用経鼻接種によるウイルス交叉防御効果[Invited]Oral presentation
- 第12回日本ワクチン学会学術集会, Nov. 2008, Japanese, 日本ワクチン学会, 熊本, Domestic conferenceConstruction of a recombinant varicella vaccine expressing mumps virus hemagglutinin-neuraminidase and measles virus hemagglutinin glycoproteins.[Invited]Oral presentation
- 第56回日本ウイルス学会学術集会, Oct. 2008, Japanese, 日本ウイルス学会, 岡山, Domestic conference水痘帯状疱疹ウイルスpOka株とvOka株におけるORF0遺伝子産物の解析[Invited]Oral presentation
- 第56回日本ウイルス学会学術集会, Oct. 2008, Japanese, 日本ウイルス学会, 岡山, Domestic conference水痘帯状疱疹ウイルスORF49と結合するウイルス性因子の同定および解析[Invited]Oral presentation
- 第56回日本ウイルス学会学術集会, Oct. 2008, Japanese, 日本ウイルス学会, 岡山, Domestic conferenceヒトヘルペスウイルス６前初期プロモーターを応用した外来遺伝子発現用プロモーターの構築[Invited]Poster presentation
- 第56回日本ウイルス学会学術集会, Oct. 2008, Japanese, 日本ウイルス学会, 岡山, Domestic conferenceヒトヘルペスウイルス６エンベロープ糖タンパク glycoprotein M のウイルス感染における解析[Invited]Poster presentation
- 第56回日本ウイルス学会学術集会, Oct. 2008, Japanese, 日本ウイルス学会, 岡山, Domestic conferenceアジュバント-日本脳炎ワクチンの1回接種での防御免疫応答の持続性と免疫学的機構[Invited]Oral presentation
- 第56回日本ウイルス学会学術集会, Oct. 2008, Japanese, 日本ウイルス学会, 岡山, Domestic conferenceBAC法を用いた水痘帯状疱疹ウイルス（VZV）ワクチン株からのクローン単離とその増殖性の比較[Invited]Oral presentation
- The 8th Awaji International Forum on Infection and Immunity, Sep. 2008, English, International Forum on Infection and Immunity, 淡路, International conferenceTraining Course 3 (Virology)[Invited]Others
- The 8th Awaji International Forum on Infection and Immunity, Sep. 2008, English, International Forum on Infection and Immunity, 淡路, International conferenceHuman herpesvirus-6 infection induces the reorganization of membrane microdomains in target cells, which are required for virus entry.[Invited]Poster presentation
- 33rd International Herpesvirus Workshop, Jul. 2008, English, International Herpesvirus Workshop, エストリル, ポルトガル, International conferenceNewly identified posttranscriptional regulation in ORF50 gene which encodes glycoprotein M.[Invited]Poster presentation
- 33rd International Herpesvirus Workshop, Jul. 2008, English, International Herpesvirus Workshop, エストリル, ポルトガル, International conferenceConstruction of a recombinant varicella virus expressing hemagglutinin-neuraminidase and fusion glycoproteins of mumps virus.[Invited]Poster presentation
- 33rd International Herpesvirus Workshop, Jul. 2008, English, International Herpesvirus Workshop, エストリル, ポルトガル, International conferenceComparison of skin test and interferon-gamma ELISPOT assay on measurement of varicella-zoster virus (VZV)-specific cell-mediated immunity.[Invited]Poster presentation
- 第23回ヘルペスウイルス研究会, Jun. 2008, Japanese, ヘルペスウイルス研究会, 鳥取, Domestic conference水痘帯状疱疹ウイルス特異的な細胞性免疫能測定における皮内試験とIFN-gamma ELISPOT 法との比較検討[Invited]Oral presentation
- 第23回ヘルペスウイルス研究会, Jun. 2008, Japanese, ヘルペスウイルス研究会, 鳥取, Domestic conference水痘帯状疱疹ウイルスワクチン株のクローニングと性状解析[Invited]Oral presentation
- 第23回ヘルペスウイルス研究会, Jun. 2008, Japanese, ヘルペスウイルス研究会, 鳥取, Domestic conference水痘帯状疱疹ウイルス ORF0 の pOka株、vOka株間での違い[Invited]Oral presentation
- 第23回ヘルペスウイルス研究会, Jun. 2008, Japanese, ヘルペスウイルス研究会, 鳥取, Domestic conferenceヒトヘルペスウイルス６およびヒトヘルペスウイルス７の前初期プロモーター解析[Invited]Oral presentation
- 第23回ヘルペスウイルス研究会, Jun. 2008, Japanese, ヘルペスウイルス研究会, 鳥取, Domestic conferenceヒトヘルペスウイルス６ glycoprotein M の性状解析[Invited]Oral presentation
- 6th International Conference on HHV-6 & 7, Jun. 2008, English, International Conference on HHV-6 & 7, ボルチモア, アメリカ, International conferenceThe membrane microdomains of host cells are important for human herpesvirus-6 entry.[Invited]Oral presentation
- 6th International Conference on HHV-6 & 7, Jun. 2008, English, International Conference on HHV-6 & 7, ボルチモア, アメリカ, International conferenceHuman herpesvirus-6 effectively transmits from dendritic cells to CD4+ T cells.[Invited]Oral presentation
- 第23回ヘルペスウイルス研究会, Jun. 2008, Japanese, ヘルペスウイルス研究会, 鳥取, Domestic conferenceHHV-6感染による宿主細胞ラフトの重要性[Invited]Oral presentation
- 6th International Conference on HHV-6 & 7, Jun. 2008, English, International Conference on HHV-6 & 7, ボルチモア, アメリカ, International conferenceHHV-6 virion assembly and egress.[Invited]Invited oral presentation
- THE JAPANESE BIOLOGICAL SAFETY ASSOCIATION
- THE MOLECULAR BIOLOGY SOCIETY OF JAPAN
- THE JAPANESE SOCIETY FOR VACCINOLOGY
- THE JAPANESE SOCIETY FOR VIROLOGY
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Nara Medical University, 01 Apr. 2021 - 31 Mar. 2024Elucidation of the pathogenic mechanism of autoimmune diseases focusing on HHV-6 persistent infection in DIHS薬剤性過敏症症候群（DIHS）は多臓器障害を伴う重症薬疹の一つである。経過中にHHV-6の再活性化を生じ、症状の遷延化、重症化に関わっている。本疾患のもう一つの特徴は、回復期にⅠ型糖尿病、慢性甲状腺炎などの自己免疫性疾患を発症することであるが、その機序は不明である。 われわれはこれまでにDIHSにおけるHHV-6持続感染患者では、回復期に高率に自己免疫性疾患を発症することを見出したが、この事実を踏まえて、本研究ではHHV-6持続感染が患者の免疫状態におよぼす影響を明らかにすることにより、DIHS後の自己免疫疾患の発症機序の解明を目指している。 今回の研究では、まずDIHS後にHHV-6の持続感染をきたした患者について、持続感染期におけるHHV-6感染の局在を解析した。その結果、HHV-6は主にCD4 central memory T細胞に持続感染していることが明らかになった。 次に、DIHS後に自己免疫疾患を発症したHHV-6持続感染群と、合併症をみとめなかった一過性感染群について、急性期と回復期のPBMCを用いてscRNA-seqを行い、両群の各病期における免疫細胞サブセットの変遷、免疫細胞ごとの遺伝子発現の変遷を解析した。その結果、一過性感染群急性期にはCD14 単球系細胞の増加および活性化がみられたのに対して、持続感染群急性期では単球系細胞の増加・活性化はほとんどみられず、発症早期の単球系細胞の反応性の低下がその後のHHV-6持続感染に関わっている可能性が示唆された。 また、持続感染期におけるHHV-6の主なreservoirであるCD4 central memory T細胞では免疫関連遺伝子を含む複数の遺伝子が特異的に発現亢進していることが明らかになり、この細胞の自己免疫疾患発症への関与ならびに今回同定された遺伝子のHHV-6持続感染への関与が推測された。
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Special Purposes, Nagasaki University, 20 Feb. 2020 - 31 Mar. 2021Urgent research on COVID-19 utilizing infectious disease research stations in AsiaA novel COVID-19 diagnostic system that was developed using the LAMP method has been utilized in epidemic situations such as a COVID-19 outbreak on a cruise ship in Japan. In addition to this diagnostic system, a serological diagnostic ELISA system has also been developed using a genetically engineered viral N protein. The sensitivity and specificity of the ELISA system were 91.1% and 93.8% respectively, and it has been successfully employed nationally in Vietnam during outbreak control activities. Conventional virus neutralization tests need to use live viruses, which are pathogenic. We therefore developed a pseudo-virus system in order to safely measure virus neutralizing antibodies. We also conducted a molecular epidemiological study using a full-genome analysis of SARS-CoV-2 strains on a region wide scale and found that a variant, Q667H was expanding in Indonesia. This suggests the importance of continuous virus genome surveillance worldwide for better vigilance and management.
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Nara Medical University, 01 Apr. 2014 - 31 Mar. 2017Study on HHV6 reactivation mechanism in DIHS focusing on virus-derived chemokine receptorHHV-6 reactivation is involved in the pathogenesis of drug-induced hypersensitivity syndrome (DIHS), but the reactivation mechanism is still unclear. In this study, we aimed to elucidate the mechanism of HHV-6 reactivation focusing on the marked elevation of Th2-related chemokine (TARC) in the acute phase of DIHS and the fact that HHV-6 has TARC receptor. As a result, we found that HHV-6 receptor (CD134) markedly increased on the T cell surface correlated with the elevation of serum TARC level in the acute phase of DIHS, and that blood HHV-6 DNA amount was also correlated with serum TARC level. These findings suggested that increased expression of CD134 associated with elevated TARC might be involved in HHV-6 reactivation in vivo.
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2014 - 31 Mar. 2017Pathogenic microorganism identification in neonatal infectious diseases by a meta-genomic analysis using the next generation sequencerThe purpose of this study was to establish a meta-genomic analysis using the next generation sequencer for perinatal and neonatal infectious diseases, and to identify pathogenic microorganisms that had been difficult to identify to date. As results, a meta-genomic analysis system using the next generation sequencer was established during the study period and we applied to the neonatal and pediatric patients with infection. We obtained new findings from patient specimens using these techniques, and for the first time, reported the cases to the international journals, such as a newborn with persistent pulmonary hypertension who was detected echovirus 7 from not only the serum, nasal swab and bronchoalveolar lavage, but also the preserved umbilical cord, a pediatric patient due to enterovirus D68 infection that developed interstitial pneumonia, and a newborn with congenital cytomegalovirus infection with retinal arterio-venous anastomosis.
- 学術研究助成基金助成金／挑戦的萌芽研究, Apr. 2015 - Mar. 2017, Principal investigatorCompetitive research funding
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Osaka Medical College, 01 Apr. 2012 - 31 Mar. 2016Varicella zoster virus-specific cell-mediated immunity in patients with facial nerve paralysisWe determined the median spot numbers and examined varicella zoster virus (VZV)-specific cell-mediated immunity (CMI) in patients with Hunt syndrome and with Bell's palsy using IFN-γ enzyme-linked immunospot (ELISPOT) assays. We analyzed the relationship between the value of VZV-specific CMI and days from disease onset. The median spot number in Hunt syndrome (87.3) was higher than that in Bell's palsy (62.3). Hunt syndrome showed a strong relationship between the ELISPOT count and days from onset. Within the first 5 days from onset, no ELISPOT counts higher than 80 were observed. These results suggest that VZV-specific CMI in Hunt syndrome is low at disease onset and increases rapidly thereafter. Consequently, reduced VZV-specific CMI may play an important role in the reactivation of VZV in the facial nerve, leading to Hunt syndrome
- 国立研究開発法人日本医療研究開発機構, 医療分野研究成果展開事業 産学連携医療イノベーション創出プログラム(ACT-MS), 2016, Principal investigator（AMED）小児において疾病負荷が高い突発性発疹ウイルス感染症に対する新規ワクチン開発Competitive research funding
- 国立研究開発法人日本医療研究開発機構, 新興・再興感染症に対する革新的医薬品等開発推進研究事業, 2016, Principal investigator（AMED）ワクチンによって予防可能な疾患のサーベイランス強化と新規ワクチンの創出等に関する研究Competitive research funding
- 国立研究開発法人日本医療研究開発機構, 感染症研究国際展開戦略プログラム, 2016, Principal investigatorインドネシアにおける新興・再興感染症の国際共同研究拠点形成Competitive research funding
- 文部科学省, 大学の世界展開力強化事業, 2016, Principal investigatorASEAN諸国との連携・協働による次世代医学・保健学グローバルリーダーの育成Competitive research funding
- 科学研究費補助金／基盤研究(B), Apr. 2012 - Mar. 2015, Principal investigatorCompetitive research funding
- 日本医療研究開発機構, 日本医療研究開発機構研究費（旧厚生科研）, 2015, Principal investigator（旧厚生科研）利便性の高い五種混合ワクチンの開発に向けた研究Competitive research funding
- 大学の世界展開力強化事業, 2015, Principal investigator世界展開力「ASEAN諸国との連携・協働による次世代医学・保健学グローバルリーダーの育成」Competitive research funding
- 日本医療研究開発機構, 感染症研究国際展開戦略プログラム, 2015, Principal investigatorJ-GRID「インドネシアにおける新興・再興感染症の国際共同研究拠点形成」Competitive research funding
- 国立研究開発法人日本医療研究開発機構, 感染症実用化研究事業 新興・再興感染症に対する革新的医薬品等開発推進研究事業, 2015, Principal investigator(AMED)ワクチンによって予防可能な疾患のサーベイランス強化と新規ワクチンの創出等に関する研究Competitive research funding
- 科学研究費補助金／萌芽研究, Apr. 2012 - Mar. 2014, Principal investigatorCompetitive research funding
- 厚生労働科学研究費補助金, 2014, Principal investigator厚生科研「利便性の高い五種混合ワクチンの開発に向けた研究」Competitive research funding
- 厚生労働科学研究費補助金, 2014, Principal investigator厚生科研「ワクチン基礎生産技術の向上に関する研究」Competitive research funding
- 厚生労働科学研究費補助金, 2013, Principal investigator厚生科研「利便性の高い五種混合ワクチンの開発に向けた研究」Competitive research funding
- 厚生労働科学研究費補助金, 2013, Principal investigator厚生科研「ワクチン基礎生産技術の向上に関する研究」Competitive research funding
- 厚生労働科学研究費補助金, 2012, Principal investigator厚生科研「ワクチン基礎生産技術の向上に関する研究」Competitive research funding
- 2010, Principal investigator厚生科研「臓器移植患者の予後およびQOLの向上のための真菌やウイルス感染症の予防・診断・治療に関する研究」Competitive research funding
- 2010, Principal investigator厚生科研「ワクチン戦略による麻疹および先天性風疹症候群の排除、およびワクチンで予防可能疾患の疫学並びにワクチンの有用性に関する基礎的臨床的研究」Competitive research funding
- 2009, Principal investigator厚生科研「臓器移植患者の予後およびＱＯＬの向上のため真菌やウィルス感染症の予防・診断・治療に関する研究」Competitive research funding
- 2009, Principal investigator厚生科研「ワクチン戦略による麻疹および先天性風疹症候群の排除、およびワクチンで予防可能疾患の疫学ならびにワクチンの有用性に関する基礎的臨床的研究」Competitive research funding
- 科学研究費補助金／特定領域研究, 2009, Principal investigatorCompetitive research funding
- 日本学術振興会, 科学研究費助成事業, 特定領域研究, 2007 - 2008ヒトヘルペスウイルス6エンベロープ糖タンパク質の機能解析による感染機構解明ヒトヘルペスウイルス6(HHV-6)は、βヘルペスウイルスであり、T細胞において感染増殖することができる。HHV-6は、塩基配列、抗原性、細胞向性などの違いから二つのバリアント, HHV-6AおよびHHV-6Bに分けられている。HHV-6Bは突発性発疹の原因ウイルスである。今回、我々はHHV-6Aを用いて下記の事象を明らかにした。 1. 電子顕微鏡的観察により、HHV-6はT細胞に感染することによって細胞のバルーニングを誘導し、感染細胞内に多数のmultivesicular body(MVB)を形成した。MVB形成は、非感染細胞においては認められなかった。 2. 感染細胞で形成されたMVB内には多数の小胞に加え、多数の成熟ウイルス粒子が認められた。さらに、成熟ウイルス粒子上には、MVBのマーカーであるCD63が検出された。 3. MVB内の小胞にはウイルスエンベロープ糖タンパク質であるgBおよびgMが検出された。 4. 未熟ウイルス粒子が、TGNおよびendosomeの性質をもった小胞膜に出芽する像が観察された。 5. MVB膜と細胞形質膜が融合し、MVB内の小胞およびウイルス粒子が細胞外へ放出される像が観察された。 以上によりHHV-6は、TGNおよびendosomeの性質をもった小胞膜に出芽することにより、成熟ウイルス粒子となること、そしてその小胞膜は次第にMVBへと変化し、最終的には、MVBの膜とに質膜が融合することによってウイルスは細胞外へ放出されることが明らかになった。 また、我々は、HHV-6感染において宿主の細胞膜に存在するコレステロールがウイルス感染に必須であることを明らかにした。つまり、膜上のコレステロールは、ウイルスが宿主細胞へ侵入する際のウイルスエンベロープと細胞膜の融合過程に特に重要であることを明らかにした。
- 2008, Principal investigator厚生科研「予防接種で予防可能疾患の今後の感染症対策に必要な予防接種に関する研究」Competitive research funding
- 2008, Principal investigator厚生科研「臓器移植や悪性腫瘍による免疫低下状態で発生するウィルス感染症の予防と治療に関する研究」Competitive research funding
- 科学研究費補助金／特定領域研究, 2008, Principal investigatorCompetitive research funding
- 科学研究費補助金／基盤研究(B), 2008, Principal investigatorCompetitive research funding
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), NATIONAL INSTITUTE OF BIOMEDICAL INNOVATION, 2005 - 2006ANALYSIS OF MATURATION AND EGRESS OF HUMAN HERPES VIRUSESWe analyzed the characterization of human herpesviruses in infected cells, and we got the results. The results are shown below ; 1.Human herpesvirus 6 (HHV-6) envelope cholesterol was found to be required for virus entry, especially fusion process in entry. The result also indicates that the envelope cholesterol possibly plays an important role for virus maturation as well as entry process. 2.Human herpesvirus 7 (HHV-7) encoded U47 proteins whose sizes were 49 and 51kDa, were digested with endo H and endo F, and incorporated into virions, indicating that U47 gene products are envelope glycoproteins modified with N-linked oligosaccharides. Furthermore, U47 proteins interacted with gH and gL in infected cells, indicating that U47 proteins may play roles for entry, virion maturation or egress process. 3.HHV-7 encodes two functional chemokine receptors in the U12 and U51 genes. The cellular ligands for these receptors are, respectively, MDC/CCL22 (the ligand for CCR4), and ELC/CCL19 (the ligand for CCR7). The mouse cells co-expressing CCR4 or CCR7 and U12 responded to both MDC/CCL22 and ELC/CCL19 in a calcium mobilization assay. The similar results were obtained with mouse cells co-expressing CCR4 or CCR7 with U51. These results suggest that the HHV-7 U12 and U51 receptors can function in concert with CCR4 and 12 CCR7 in host cell signaling pathways. 4.HHV-7 infection caused elevation of CRPs, CD46 and CD59, which may be a possible mechanism for HHV-7 to evade humoral immunity via complement.
- 日本学術振興会, 科学研究費助成事業, 特定領域研究, 2004 - 2005ヒトヘルペスウイルス6の宿主細胞へのエントリー機構の解明ヒトヘルペスウイルス6(HHV-6)は、Tリンパ球向性のウイルスであり、βヘルペスウイルスに属する。現在では、塩基配列や抗原性の違いにより、二つのバリアントに分けられている(HHV-6A,HHV-6B)。HHV-6Bは突発性発疹の原因ウイルスであるが、HHV-6Aに関してはその病態は不明である。本研究は、HHV-6の宿主細胞へのエントリー機構に関わる因子を探索し、その機序を解析することを目的とする。本年度の成果を以下に記す。 1.HHV-6ウイルスエンベロープを構成するコレステロールを薬剤処理によって除去することにより、HHV-6の細胞内への感染およびHHV-6が引き起こす細胞膜融合が阻害された。しかし、ウイルス粒子自体の細胞への結合は完全には阻害されなかった。gH/gL/gQ1/gQ2複合体(HHV-6リガンド)のヒトCD46(宿主レセプター)への結合も完全には阻害されなかった。 2.薬剤処理によってもウイルスエンベロープに存在する糖タンパクの複合体(gH/gL/gQ1/gQ2およびgBの二量体)に変化は認められなかった。 3.以上の結果より、ウイルスエンベロープを構成するコレステロールはウイルスの宿主細胞への侵入過程、特にウイルスエンベロープと細胞膜の融合過程に重要な役割を果たしていることが示唆された。この機序としてコレステロールを除くことにより、エンベロープに存在する糖タンパクの基盤が緩みウイルスの宿主細胞への結合後に起こる糖タンパクの構造変化が起こらず、そのため膜融合ができなくなる可能性が考えられた。 ウイルス粒子上のコレステロールの宿主細胞への侵入過程での重要性が示唆され、本結果は、HHV-6感染症の治療法開発に繋がる可能性があり、意義深いと考えられる。
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Osaka University, 2003 - 2004Identification of cellular receptor and its ligand for human herpesvirus 6We have studied about the cellular receptors and the ligand(s) of human herpes virus 6 (HHV-6). During the time, we found as follows. (1)HHV-6 gQ gene encodes an additional product whose mature molecular mass is 37kDa (gQ-37K), and which is derived from a different transcript. (2)We designated gQ-80K as gQl and gQ37K as gQ2. (3)The gQ2 also interacts with the gH/gL/gQ1 complex in HHV-6 infected cells and virions. (4)The gQ2 and gQ1 interact in the endoplasmic reticulum, however, gH/gL/gQ1/gQ2 heterotetrameric complex arises in post endoplasmic reticulum compartment, and the mature complex is subsequently incorporated into viral particles. (5)The heterotetrameric complex is viral ligand for HHV-6 cellular receptor, human CD46. (6)HHV-6 gO gene encodes a third component of HHV-6 gH/gL containing envelope complex. (7)The gH/gL/gO complex does not bind to human CD46, indicating that the complex is not ligand for human CD46. (8)The gH/gL/gO and gH/gL/gQ1/gQ2 complexes express in virions independently. (9)These results indicate that the gH/gL/gO complex may play a role different from that of gH/gL/gQ1/gQ2 during viral infection. (10)This is a first report of two kinds of gH/gL complexes on the viral envelope in a member of the herpesvirus family.
- 日本学術振興会, 科学研究費助成事業, 特定領域研究, 大阪大学, 2002 - 2002ヘルペスウイルスの潜伏感染・再活性化の機構解析β-ヘルペスウイルスに属するヒトヘルペスウイルス(HHV)-6と、γ-ヘルペスウイルスに属するHHV-8に関して、潜伏感染機構の解析を行い、以下の結果を得た。 1.HHV-6の潜伏感染時に特異的に発現する遺伝子および蛋白を同定した。この遺伝子は、構造およびコードしている蛋白が、同じβ-ヘルペスウイルスに属するヒトサイトメガロウイルスと極めて似ており、両者の潜伏感染機構が類似である事を示唆した(担当:近藤)。 2.HHV-6の潜伏感染特異的遺伝子の、発現動態とコードされる蛋白の機能を解析したところ、潜伏感染遺伝子の一部の発現と蛋白翻訳の亢進が、HHV-6の再活性化の起点となっている事が判明した(担当:近藤)。 3.また、HHV-6の潜伏感染において、2で述べた潜伏感染遺伝子の発現亢進状態は、比較的安定で、他のヘルペスウイルスの潜伏感染では知られていなかった、新しい相である事が判明した(担当:近藤)。 4.HHV-8の再活性化では、ウイルスの前初期遺伝子ORF50/RTAの発現が起点となる事が知られていた。このORF50/RTAは、強いtransactivator活性を持ち、多くのウイルス遺伝子の発現を活性化する。この遺伝子は、ウイルス遺伝子K9の発現を促進する事が知られていたが、ORF50/RTAが作用するcis-acting elementは知られていなかった。この遺伝子発現を解析し、これまでに知られていた、ORF50/RTAのcis-acting elementとは異なったものを見いだした(担当:上田)。