研究活動情報

• 2024年10月 神戸大学, 学長表彰（財務貢献）


• 2023年10月 神戸大学, 学長表彰（財務貢献）


• 2022年10月 神戸大学, 学長表彰（財務貢献）


• 2021年10月 神戸大学, 学長表彰（財務貢献）


• 2019年10月 神戸大学, 学長表彰（財務貢献）


• 2018年04月 前之園賞


• 2007年03月 APASL, Young Investigator Award

• Identification of glycogen synthase kinase 3alpha/beta as a host factor required for HBV transcription using high-throughput screening.

  Hironori Nishitsuji, Yui Naito, Yuuna Murakami, Masaya Sugiyama, Masashi Mizokami, Ikuo Shoji, Takayuki Murata, Kunitada Shimotohno

  BACKGROUND AND AIMS: HBV leads to severe liver diseases, such as cirrhosis and HCC. Identification of host factors that regulate HBV replication can provide new therapeutic targets. The discovery of sodium taurocholate cotransporting polypeptide (NTCP) as an HBV entry receptor has enabled the establishment of hepatic cell lines for analyzing HBV infection and propagation. Using this new system, studies aimed at identifying host factors that regulate HBV propagation have increased. APPROACH AND RESULTS: We established an HBV-based-reporter gene expression system that mimics HBV replication from transcription to virus egress. Using this approach, we screened 1827 Food and Drug Administration-approved compounds and identified glycogen synthase kinase 3 (GSK3)alpha/beta inhibitors, including AZD1080, CHIR-98014, CHIR-98021, BIO, and AZD2858, as anti-HBV compounds. These compounds suppressed HBeAg and HBsAg production in HBV-infected human primary hepatocytes. Proteome analysis revealed that GSK3alpha/beta phosphorylated forkhead box K1/2 (FOXK1/2)s. A double-knockout of FOXK1/2 in HBV-infected HepG2-NTCP cells reduced HBeAg and HBsAg production. The rescue of FOXK2 expression, but not FOXK1 expression, in FOXK1/2-double-knockout cells restored HBeAg and HBsAg production. Importantly, phosphorylation of FOXK2 at Ser 424 is required for GSK3alpha/beta-mediated HBeAg and HBsAg production. We observed the binding of FOXK2 to HBV DNA in HepG2-NTCP cells. CONCLUSIONS: Our recombinant HBV-based screening system enables the discovery of new targets. Using our approach, we identified GSK3 inhibitors as potential anti-HBV agents.

  2025年01月, Hepatology (Baltimore, Md.), 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Unusual G9P[4] Rotavirus Emerged After the Dynamic Changes in Rotavirus Genotypes From Equine-Like G3 to Typical Human G1/G3 in Indonesia.

  Zayyin Dinana, Yen Hai Doan, Aussie Tahta Maharani, Anisa Lailatul Fitria, Laura Navika Yamani, Juniastuti, Rury Mega Wahyuni, Soegeng Soegijanto, Soetjipto, Takako Utsumi, Chieko Matsui, Lin Deng, Nobuhiro Takemae, Tsutomu Kageyama, Kazuhiko Katayama, Maria Inge Lusida, Ikuo Shoji

  Inter-genogroup reassortment of Rotavirus A (RVA) strains has highlighted the spread of unusual RVA strains worldwide. We previously reported the equine-like G3 RVA as the predominant strain in Indonesia in 2015-2016. However, since July 2017, typical human genotypes G1 and G3 have replaced these strains completely. To understand how dynamic changes in RVA occur in Indonesia, we performed a detailed epidemiological study. A total of 356 stool specimens were collected from hospitalized children in Sidoarjo, Indonesia between 2018 and 2022. Whole-genome sequencing was performed for all 26 RVA-positive samples using next-generation sequencing. Twenty-four samples were determined to be the unusual RVA G9P[4], while two were G9P[6]. Detailed analysis revealed that seven G9P[4] strains had the typical DS-1-like backbone, while the other strains exhibited a double-reassortant profile (G9-N1) on the DS-1-like backbone. The Bayesian evolutionary analyses suggested that the Indonesian G9P[4] strains share a common ancestor with previously reported G9P[4] strains in the VP7 and VP4 genes. G9P[4] DS-1-like strains were identified as the predominant genotype in Indonesia in 2021 for the first time. These results suggest that the G9P[4] strains were generated from the previous G9P[4] strains that had undergone further intra-reassortments with the other circulating strains.

  2024年12月, Journal of medical virology, 96(12) (12), e70106, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• SARS-CoV-2 papain-like protease inhibits ISGylation of the viral nucleocapsid protein to evade host anti-viral immunity.

  Aulia Fitri Rhamadianti, Takayuki Abe, Tomohisa Tanaka, Chikako Ono, Hisashi Katayama, Yoshiteru Makino, Lin Deng, Chieko Matsui, Kohji Moriishi, Fumi Shima, Yoshiharu Matsuura, Ikuo Shoji

  A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes mild-to-severe respiratory symptoms, including acute respiratory distress. Despite remarkable efforts to investigate the virological and pathological impacts of SARS-CoV-2, many of the characteristics of SARS-CoV-2 infection still remain unknown. The interferon-inducible ubiquitin-like protein ISG15 is covalently conjugated to several viral proteins to suppress their functions. It was reported that SARS-CoV-2 utilizes its papain-like protease (PLpro) to impede ISG15 conjugation, ISGylation. However, the role of ISGylation in SARS-CoV-2 infection remains unclear. We aimed to elucidate the role of ISGylation in SARS-CoV-2 replication. We observed that the SARS-CoV-2 nucleocapsid protein is a target protein for the HERC5 E3 ligase-mediated ISGylation in cultured cells. Site-directed mutagenesis reveals that the residue K374 within the C-terminal spacer B-N3 (SB/N3) domain is required for nucleocapsid-ISGylation, alongside conserved lysine residue in MERS-CoV (K372) and SARS-CoV (K375). We also observed that the nucleocapsid-ISGylation results in the disruption of nucleocapsid oligomerization, thereby inhibiting viral replication. Knockdown of ISG15 mRNA enhanced SARS-CoV-2 replication in the SARS-CoV-2 reporter replicon cells, while exogenous expression of ISGylation components partially hampered SARS-CoV-2 replication. Taken together, these results suggest that SARS-CoV-2 PLpro inhibits ISGylation of the nucleocapsid protein to promote viral replication by evading ISGylation-mediated disruption of the nucleocapsid oligomerization.IMPORTANCEISG15 is an interferon-inducible ubiquitin-like protein that is covalently conjugated to the viral protein via specific Lys residues and suppresses viral functions and viral propagation in many viruses. However, the role of ISGylation in SARS-CoV-2 infection remains largely unclear. Here, we demonstrated that the SARS-CoV-2 nucleocapsid protein is a target protein for the HERC5 E3 ligase-mediated ISGylation. We also found that the residue K374 within the C-terminal spacer B-N3 (SB/N3) domain is required for nucleocapsid-ISGylation. We obtained evidence suggesting that nucleocapsid-ISGylation results in the disruption of nucleocapsid-oligomerization, thereby suppressing SARS-CoV-2 replication. We discovered that SARS-CoV-2 papain-like protease inhibits ISG15 conjugation of nucleocapsid protein via its de-conjugating enzyme activity. The present study may contribute to gaining new insight into the roles of ISGylation-mediated anti-viral function in SARS-CoV-2 infection and may lead to the development of more potent and selective inhibitors targeted to SARS-CoV-2 nucleocapsid protein.

  2024年09月, Journal of virology, 98(9) (9), e0085524, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Cellular Release of Infectious Hepatitis C Virus Particles via Endosomal Pathways.

  Lin Deng, Muchamad Ridotu Solichin, Dewa Nyoman Murti Adyaksa, Maria Alethea Septianastiti, Rhamadianti Aulia Fitri, Gede Ngurah Rsi Suwardan, Chieko Matsui, Takayuki Abe, Ikuo Shoji

  Hepatitis C virus (HCV) is a positive-sense, single-stranded RNA virus that causes chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. The release of infectious HCV particles from infected hepatocytes is a crucial step in viral dissemination and disease progression. While the exact mechanisms of HCV particle release remain poorly understood, emerging evidence suggests that HCV utilizes intracellular membrane trafficking and secretory pathways. These pathways include the Golgi secretory pathway and the endosomal trafficking pathways, such as the recycling endosome pathway and the endosomal sorting complex required for transport (ESCRT)-dependent multivesicular bodies (MVBs) pathway. This review provides an overview of recent advances in understanding the release of infectious HCV particles, with a particular focus on the involvement of the host cell factors that participate in HCV particle release. By summarizing the current knowledge in this area, this review aims to contribute to a better understanding of endosomal pathways involved in the extracellular release of HCV particles and the development of novel antiviral strategies.

  2023年12月, Viruses, 15(12) (12), 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Oxidative stress sensor Keap1 recognizes HBx protein to activate the Nrf2/ARE signaling pathway, thereby inhibiting hepatitis B virus replication.

  Adi Ariffianto, Lin Deng, Takayuki Abe, Chieko Matsui, Masahiko Ito, Akihide Ryo, Hussein Hassan Aly, Koichi Watashi, Tetsuro Suzuki, Masashi Mizokami, Yoshiharu Matsuura, Ikuo Shoji

  Hepatitis B virus (HBV) infection promotes reactive oxygen species production while paradoxically inducing the expression of antioxidant enzymes. HBV-induced disorders of redox homeostasis are closely associated with the development of hepatic diseases. However, the molecular mechanisms underlying the HBV-induced antioxidant response are poorly understood. The NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway is an intrinsic defense mechanism against oxidative stress. We here aim to elucidate the role of the Nrf2/ARE signaling pathway in the HBV life cycle. ARE-driven reporter assays revealed that expression of HBV X protein (HBx), but not HBV core, large HBV surface, or HBV polymerase, strongly enhanced ARE-luciferase activity, suggesting that HBx plays an important role in the HBV-induced antioxidant response. Knockdown of Nrf2 resulted in a marked decrease in HBx-induced ARE-luciferase activity. Immunoblot analysis and immunofluorescence staining suggested that HBx activates Nrf2 by increasing Nrf2 protein levels and enhancing Nrf2 nuclear localization. The oxidative stress sensor Kelch-like ECH-associated protein 1 (Keap1) is required for the ubiquitin-dependent degradation of Nrf2. Coimmunoprecipitation analysis revealed that HBx interacted with Keap1, suggesting that HBx competes with Nrf2 for interaction with Keap1. A cell-based ubiquitylation assay showed that HBx promoted polyubiquitylation of Nrf2 via K6-linked polyubiquitin chains, and that this action may be associated with Nrf2 stabilization. A chromatin immunoprecipitation assay suggested that Nrf2 interacts with the HBV core promoter. Overexpression of Nrf2 strongly suppressed HBV core promoter activity, resulting in a marked reduction in viral replication. Based on the above, we propose that Keap1 recognizes HBx to activate the Nrf2/ARE signaling pathway upon HBV infection, thereby inhibiting HBV replication.IMPORTANCEThe Kelch-like ECH-associated protein 1 (Keap1)/NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway is one of the most important defense mechanisms against oxidative stress. We previously reported that a cellular hydrogen peroxide scavenger protein, peroxiredoxin 1, a target gene of transcription factor Nrf2, acts as a novel HBV X protein (HBx)-interacting protein and negatively regulates hepatitis B virus (HBV) propagation through degradation of HBV RNA. This study further demonstrates that the Nrf2/ARE signaling pathway is activated during HBV infection, eventually leading to the suppression of HBV replication. We provide evidence suggesting that Keap1 interacts with HBx, leading to Nrf2 activation and inhibition of HBV replication via suppression of HBV core promoter activity. This study raises the possibility that activation of the Nrf2/ARE signaling pathway is a potential therapeutic strategy against HBV. Our findings may contribute to an improved understanding of the negative regulation of HBV replication by the antioxidant response.

  2023年10月, Journal of virology, 97(10) (10), e0128723, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• A household survey of intrafamily norovirus transmission.

  Juniastuti, Takako Utsumi, Laura Navika Yamani, Zayyin Dinana, Emily Gunawan, Aussie Tahta Maharani, Anisa Lailatul Fitria, Rury M Wahyuni, Soetjipto, Yen Hai Doan, Hiroyuki Shimizu, Koji Ishii, Chieko Matsui, Lin Deng, Takayuki Abe, Kazuhiko Katayama, Maria Inge Lusida, Ikuo Shoji

  Norovirus (NoV) is a leading cause of epidemic and sporadic gastroenteritis in people of all ages. Humans are the primary source of NoV and household contact is one of the risk factors for NoV transmission. However, the mechanisms underlying person-to-person NoV transmission are poorly understood. Here we conducted a survey to profile the frequency and characteristics of intrafamily NoV transmission. Stool samples were collected every week from three households between 2016 and 2020; the total number of samples was 1105. The detection of NoV and the genotyping were performed by reverse transcription-polymerase chain reaction targeting the capsid region and direct sequencing methods. NoV was detected in 3.4% of all samples. Eight NoV genotypes were identified. The most common genotype was GII.17, followed in order by GII.6, GI.6, GII.4, GI.3, and GI.2/GI.8/GI.9. Most NoV-positive samples were obtained from asymptomatic individuals. The highest number of NoV transmissions was found in household 3 (6 infections), followed by household 2 (2 infections), while household 1 had no NoV transmission, suggesting that asymptomatic NoV carriers play a major role in infection as NoV reservoirs in the households. Further clarification of the mode of infection will contribute to improved understanding and an appropriate prevention.

  2023年10月, Journal of medical virology, 95(10) (10), e29164, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Transcription Factor JunB Suppresses Hepatitis C Virus Replication.

  Adi Ariffianto, Lin Deng, Saki Harada, Yujiao Liang, Chieko Matsui, Takayuki Abe, Ikuo Shoji

  We previously reported that hepatitis C virus (HCV) infection activates the reactive oxygen species (ROS)/c-Jun N-terminal kinase (JNK) signaling pathway. Activation of JNK contributes to the development of liver diseases, including metabolic disorders, steatosis, liver cirrhosis and hepatocellular carcinoma. JNK is known to have numerous target genes, including JunB, a member of activator protein-1 transcription factor family. However, the roles of JunB in the HCV life cycle and HCV-associated pathogenesis remain unclear. To clarify a physiological role of JunB in HCV infection, we investigated the phosphorylation of JunB in HCV J6/JFH1-infected Huh-7.5 cells. Immunoblot analysis revealed that HCV-induced ROS/JNK activation promoted phosphorylation of JunB. The small interfering RNA (siRNA) knockdown of JunB significantly increased the amount of intracellular HCV RNA as well as the intracellular and extracellular HCV infectivity titers. Conversely, overexpression of JunB significantly reduced the amount of intracellular HCV RNA and the intracellular and extracellular HCV infectivity titers. These results suggest that JunB plays a role in inhibiting HCV propagation. Additionally, HCV-mediated JunB activation promoted hepcidin promoter activity and hepcidin mRNA levels, a key factor in modulating iron homeostasis, suggesting that JunB is involved in HCV-induced transcriptional upregulation of hepcidin. Taken together, we propose that the HCV-induced ROS/JNK/JunB signaling pathway plays roles in inhibiting HCV replication and contributing to HCV-mediated iron metabolism disorder.

  2023年08月, The Kobe journal of medical sciences, 69(3) (3), E86-E95, 英語, 国内誌

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Role of hepcidin upregulation and proteolytic cleavage of ferroportin 1 in hepatitis C virus-induced iron accumulation.

  Kazuyoshi Ohta, Masahiko Ito, Takeshi Chida, Kenji Nakashima, Satoshi Sakai, Yumi Kanegae, Hideya Kawasaki, Takuya Aoshima, Shuji Takabayashi, Hirotaka Takahashi, Kazuhito Kawata, Ikuo Shoji, Tatsuya Sawasaki, Takafumi Suda, Tetsuro Suzuki

  Hepatitis C virus (HCV) is a pathogen characterized not only by its persistent infection leading to the development of cirrhosis and hepatocellular carcinoma (HCC), but also by metabolic disorders such as lipid and iron dysregulation. Elevated iron load is commonly observed in the livers of patients with chronic hepatitis C, and hepatic iron overload is a highly profibrogenic and carcinogenic factor that increases the risk of HCC. However, the underlying mechanisms of elevated iron accumulation in HCV-infected livers remain to be fully elucidated. Here, we observed iron accumulation in cells and liver tissues under HCV infection and in mice expressing viral proteins from recombinant adenoviruses. We established two molecular mechanisms that contribute to increased iron load in cells caused by HCV infection. One is the transcriptional induction of hepcidin, the key hormone for modulating iron homeostasis. The transcription factor cAMP-responsive element-binding protein hepatocyte specific (CREBH), which was activated by HCV infection, not only directly recognizes the hepcidin promoter but also induces bone morphogenetic protein 6 (BMP6) expression, resulting in an activated BMP-SMAD pathway that enhances hepcidin promoter activity. The other is post-translational regulation of the iron-exporting membrane protein ferroportin 1 (FPN1), which is cleaved between residues Cys284 and Ala285 in the intracytoplasmic loop region of the central portion mediated by HCV NS3-4A serine protease. We propose that host transcriptional activation triggered by endoplasmic reticulum stress and FPN1 cleavage by viral protease work in concert to impair iron efflux, leading to iron accumulation in HCV-infected cells.

  2023年08月, PLoS pathogens, 19(8) (8), e1011591, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Hepatitis C Virus Disrupts Annexin 5-Mediated Occludin Integrity through Downregulation of Protein Kinase Cα (PKCα) and PKCη Expression, Thereby Promoting Viral Propagation.

  Takayuki Abe, Yuki Marutani, Lin Deng, Chieko Matsui, Masayoshi Fukasawa, Ryosuke Suzuki, Takaji Wakita, Yoshiharu Matsuura, Ikuo Shoji

  Annexins (ANXs) comprise a family of calcium- and phospholipid-binding proteins and are implicated in the hepatitis C virus (HCV) life cycle. Here, we demonstrate a novel role of ANX5 in the HCV life cycle. Comparative analysis by quantitative PCR in human hepatoma cells revealed that ANX2, ANX4, and ANX5 were highly expressed among the ANX family proteins. Knockdown of ANX5 mRNA resulted in marked enhancement of HCV RNA replication but had no effect on either HCV translation or assembly. Using the HCV pseudoparticle (HCVpp) system, we observed enhancement of HCVpp infectivity in ANX5 knockdown Huh-7OK1 cells, suggesting that ANX5 is involved in suppression of HCV entry. Additionally, we observed that subcellular localizations of tight-junction proteins, such as claudin 1 (CLDN1) and occludin (OCLN), were disrupted in the ANX5 knockdown cells. It was reported that HCV infection was facilitated by disruption of OCLN distribution and that proper distribution of OCLN was regulated by its phosphorylation. Knockdown of ANX5 resulted in a decrease of OCLN phosphorylation, thereby disrupting OCLN distribution and HCV infection. Further analysis revealed that protein kinase C (PKC) isoforms, including PKCα and PKCη, play important roles in the regulation of ANX5-mediated phosphorylation and distribution of OCLN and in the restriction of HCV infection. HCV infection reduced OCLN phosphorylation through the downregulation of PKCα and PKCη expression. Taken together, these results suggest that ANX5, PKCα, and PKCη contribute to restriction of HCV infection by regulating OCLN integrity. We propose a model that HCV disrupts ANX5-mediated OCLN integrity through downregulation of PKCα and PKCη expression, thereby promoting HCV propagation. IMPORTANCE Host cells have evolved host defense machinery to restrict viral infection. However, viruses have evolved counteracting strategies to achieve their infection. In the present study, we obtained results suggesting that ANX5 and PKC isoforms, including PKCα and PKCη, contribute to suppression of HCV infection by regulating the integrity of OCLN. The disruption of OCLN integrity increased HCV infection. We also found that HCV disrupts ANX5-mediated OCLN integrity through downregulation of PKCα and PKCη expression, thereby promoting viral infection. We propose that HCV disrupts ANX5-mediated OCLN integrity to establish a persistent infection. The disruption of tight-junction assembly may play important roles in the progression of HCV-related liver diseases.

  2023年06月, Journal of virology, 97(6) (6), e0065523, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Complete genome analyses of G12P[8] rotavirus strains from hospitalized children in Surabaya, Indonesia, 2017-2018.

  Laura Navika Yamani, Takako Utsumi, Yen Hai Doan, Yoshiki Fujii, Zayyin Dinana, Rury Mega Wahyuni, Emily Gunawan, Soegeng Soegijanto, Alpha Fardah Athiyyah, Subijanto Marto Sudarmo, Reza Gunadi Ranuh, Andy Darma, Soetjipto, Juniastuti, Rheza Gandi Bawono, Chieko Matsui, Lin Deng, Takayuki Abe, Hiroyuki Shimizu, Koji Ishii, Kazuhiko Katayama, Maria Inge Lusida, Ikuo Shoji

  Rotavirus A (RVA) is a major viral cause of acute gastroenteritis worldwide. G12 RVA strains have emerged globally since 2007. There has been no report of the whole genome sequences of G12 RVAs in Indonesia. We performed the complete genome analysis by the next-generation sequencing of five G12 strains from hospitalized children with acute gastroenteritis in Surabaya from 2017-2018. All five G12 strains were Wa-like strains (G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1) and were clustered into lineage-III of VP7 gene phylogenetic tree. STM430 sample was observed as a mixed-infection between G12 and G1 strains: G12/G1-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. A phylogenetic tree analysis revealed that all five Indonesian G12 strains (SOEP379, STM371, STM413, STM430, and STM433) were genetically close to each other in all 11 genome segments with 98.0-100% nucleotide identities, except VP3 and NSP4 of STM430, suggesting that these strains have originated from a similar ancestral G12 RVA. The VP3 and NSP4 genome segments of STM430-G12P[8] were separated phylogenetically from those of the other four G12 strains, probably due to intra-genotype reassortment between the G12 and G1 Wa-like strains. The change from G12P[6] lineage-II in 2007 to G12P[8] lineage-III 2017-2018 suggests the evolution and diversity of G12 RVAs in Indonesia over the past approximately 10 years. This article is protected by copyright. All rights reserved.

  2023年01月, Journal of medical virology, 95(2) (2), e28485, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Hepatitis C virus NS5A protein promotes the lysosomal degradation of diacylglycerol O-acyltransferase 1 (DGAT1) via endosomal microautophagy

  Putu Yuliandari, Chieko Matsui, Lin Deng, Takayuki Abe, Hiroyuki Mori, Shuhei Taguwa, Chikako Ono, Takasuke Fukuhara, Yoshiharu Matsuura, Ikuo Shoji

  Informa UK Limited, 2022年07月, Autophagy Reports, 1(1) (1), 264 - 285

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Hepatitis C Virus-Induced ROS/JNK Signaling Pathway Activates the E3 Ubiquitin Ligase Itch to Promote the Release of HCV Particles via Polyubiquitylation of VPS4A.

  Lin Deng, Yujiao Liang, Adi Ariffianto, Chieko Matsui, Takayuki Abe, Masamichi Muramatsu, Takaji Wakita, Masatoshi Maki, Hideki Shibata, Ikuo Shoji

  We previously reported that hepatitis C virus (HCV) infection activates the reactive oxygen species (ROS)/c-Jun N-terminal kinase (JNK) signaling pathway. However, the roles of ROS/JNK activation in the HCV life cycle remain unclear. We sought to identify a novel role of the ROS/JNK signaling pathway in the HCV life cycle. Immunoblot analysis revealed that HCV-induced ROS/JNK activation promoted phosphorylation of Itch, a HECT-type E3 ubiquitin ligase, leading to activation of Itch. The small interfering RNA (siRNA) knockdown of Itch significantly reduced the extracellular HCV infectivity titers, HCV RNA, and HCV core protein without affecting intracellular HCV infectivity titers, HCV RNA, and HCV proteins, suggesting that Itch is involved in the release of HCV particles. HCV-mediated JNK/Itch activation specifically promoted polyubiquitylation of an AAA-type ATPase, VPS4A, but not VPS4B, required to form multivesicular bodies. Site-directed mutagenesis revealed that two lysine residues (K23 and K121) on VPS4A were important for VPS4A polyubiquitylation. The siRNA knockdown of VPS4A, but not VPS4B, significantly reduced extracellular HCV infectivity titers. Coimmunoprecipitation analysis revealed that HCV infection specifically enhanced the interaction between CHMP1B, a subunit of endosomal sorting complexes required for transport (ESCRT)-III complex, and VPS4A, but not VPS4B, whereas VPS4A K23R/K121R greatly reduced the interaction with CHMP1B. HCV infection significantly increased ATPase activity of VPS4A, but not VPS4A K23R/K121R or VPS4B, suggesting that HCV-mediated polyubiquitylation of VPS4A contributes to activation of VPS4A. Taken together, we propose that the HCV-induced ROS/JNK/Itch signaling pathway promotes VPS4A polyubiquitylation, leading to enhanced VPS4A-CHMP1B interaction and promotion of VPS4A ATPase activity, thereby promoting the release of HCV particles. IMPORTANCE The ROS/JNK signaling pathway contributes to liver diseases, including steatosis, metabolic disorders, and hepatocellular carcinoma. We previously reported that HCV activates the ROS/JNK signaling pathway, leading to the enhancement of hepatic gluconeogenesis and apoptosis induction. This study further demonstrates that the HCV-induced ROS/JNK signaling pathway activates the E3 ubiquitin ligase Itch to promote release of HCV particles via polyubiquitylation of VPS4A. We provide evidence suggesting that HCV infection promotes the ROS/JNK/Itch signaling pathway and ESCRT/VPS4A machinery to release infectious HCV particles. Our results may lead to a better understanding of the mechanistic details of HCV particle release.

  2022年03月, Journal of virology, 96(6) (6), e0181121, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• The kinesin KIF4 mediates HBV/HDV entry through the regulation of surface NTCP localization and can be targeted by RXR agonists in vitro.

  Sameh A Gad, Masaya Sugiyama, Masataka Tsuge, Kosho Wakae, Kento Fukano, Mizuki Oshima, Camille Sureau, Noriyuki Watanabe, Takanobu Kato, Asako Murayama, Yingfang Li, Ikuo Shoji, Kunitada Shimotohno, Kazuaki Chayama, Masamichi Muramatsu, Takaji Wakita, Tomoyoshi Nozaki, Hussein H Aly

  Intracellular transport via microtubule-based dynein and kinesin family motors plays a key role in viral reproduction and transmission. We show here that Kinesin Family Member 4 (KIF4) plays an important role in HBV/HDV infection. We intended to explore host factors impacting the HBV life cycle that can be therapeutically addressed using siRNA library transfection and HBV/NLuc (HBV/NL) reporter virus infection in HepG2-hNTCP cells. KIF4 silencing resulted in a 3-fold reduction in luciferase activity following HBV/NL infection. KIF4 knockdown suppressed both HBV and HDV infection. Transient KIF4 depletion reduced surface and raised intracellular NTCP (HBV/HDV entry receptor) levels, according to both cellular fractionation and immunofluorescence analysis (IF). Overexpression of wild-type KIF4 but not ATPase-null KIF4 mutant regained the surface localization of NTCP and significantly restored HBV permissiveness in these cells. IF revealed KIF4 and NTCP colocalization across microtubule filaments, and a co-immunoprecipitation study revealed that KIF4 interacts with NTCP. KIF4 expression is regulated by FOXM1. Interestingly, we discovered that RXR agonists (Bexarotene, and Alitretinoin) down-regulated KIF4 expression via FOXM1-mediated suppression, resulting in a substantial decrease in HBV-Pre-S1 protein attachment to HepG2-hNTCP cell surface and subsequent HBV infection in both HepG2-hNTCP and primary human hepatocyte (PXB) (Bexarotene, IC50 1.89 ± 0.98 μM) cultures. Overall, our findings show that human KIF4 is a critical regulator of NTCP surface transport and localization, which is required for NTCP to function as a receptor for HBV/HDV entry. Furthermore, small molecules that suppress or alleviate KIF4 expression would be potential antiviral candidates targeting HBV and HDV entry.

  2022年03月, PLoS pathogens, 18(3) (3), e1009983, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• HERC5 E3 ligase mediates ISGylation of hepatitis B virus X protein to promote viral replication.

  Rheza Gandi Bawono, Takayuki Abe, Mengting Qu, Daisuke Kuroki, Lin Deng, Chieko Matsui, Akihide Ryo, Tetsuro Suzuki, Yoshiharu Matsuura, Masaya Sugiyama, Masashi Mizokami, Kunitada Shimotohno, Ikuo Shoji

  Ubiquitin and ubiquitin-like protein modification play important roles in modulating the functions of viral proteins in many viruses. Here we demonstrate that hepatitis B virus (HBV) X protein (HBx) is modified by ISG15, which is a type I IFN-inducible, ubiquitin-like protein; this modification is called ISGylation. Immunoblot analyses revealed that HBx proteins derived from four different HBV genotypes accepted ISGylation in cultured cells. Site-directed mutagenesis revealed that three lysine residues (K91, K95 and K140) on the HBx protein, which are well conserved among all the HBV genotypes, are involved in acceptance of ISGylation. Using expression plasmids encoding three known E3 ligases involved in the ISGylation to different substrates, we found that HERC5 functions as an E3 ligase for HBx-ISGylation. Treatment with type I and type III IFNs resulted in the limited suppression of HBV replication in Hep38.7-Tet cells. When cells were treated with IFN-α, silencing of ISG15 resulted in a marked reduction of HBV replication in Hep38.7-Tet cells, suggesting a role of ISG15 in the resistance to IFN-α. In contrast, the silencing of USP18 (an ISG15 de-conjugating enzyme) increased the HBV replication in Hep38.7-Tet cells. Taken together, these results suggest that the HERC5-mediated ISGylation of HBx protein confers pro-viral functions on HBV replication and participates in the resistance to IFN-α-mediated antiviral activity.

  2021年10月, The Journal of general virology, 102(10) (10), 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• NS5A-ISGylation via Lysine 26 Has a Critical Role for Efficient Propagation of Hepatitis C Virus Genotype 2a.

  Rheza Gandi Bawono, Takayuki Abe, Yasuaki Shibata, Chieko Matsui, Lin Deng, Ikuo Shoji

  We previously reported that hepatitis C virus (HCV) NS5A (1b, Con1) protein accepts covalent ISG15 conjugation at specific lysine (Lys) residues (K44, K68, K166, K215 and K308), exhibiting proviral effects on HCV RNA replication. Here we investigated a role of NS5A-ISGylation via Lys residues in HCV propagation using HCV infectious clone. The alignment of amino acid sequences revealed that 5 Lys residues (K20, K26, K44, K139, and K166) of the 13 Lys residues within NS5A (genotype 2a, JFH1 strain) were conserved compared to those of HCV (genotype 1b, Con1 strain). The cell-based ISGylation assay revealed that the K26 residue in the amphipathic helix (AH) domain and the K139 residue in domain I of NS5A (2a, JFH1) had the potential to accept ISGylation. Use of the HCV replicon carrying luciferase gene revealed that the K26 residue but not K139 residue of NS5A (2a, JFH1) was important for HCV RNA replication. Furthermore, cell culture HCV revealed that the mutation with the K26 residue in combination with K139 or K166 on NS5A (2a, JFH1) resulted in complete abolishment of viral propagation, suggesting that the K26 residue collaborates with either the K139 residue or K166 residue for efficient HCV propagation. Taken together, these results suggest that HCV NS5A protein has the potential to accept ISGylation via specific Lys residues, involving efficient viral propagation in a genotype-specific manner.

  2021年09月, The Kobe journal of medical sciences, 67(2) (2), E38-E47, 英語, 国内誌

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Prevalence and Distribution of Rotavirus Genotypes Among Children With Acute Gastroenteritis in Areas Other Than Java Island, Indonesia, 2016–2018

  Rury Mega Wahyuni, Takako Utsumi, Zayyin Dinana, Laura Navika Yamani, Laura Navika Juniastuti, Ishak Samuel Wuwuti, Elsa Fitriana, Emily Gunawan, Yujiao Liang, Fitratul Ramadhan, Fitratul Soetjipto, Maria Inge Lusida, Ikuo Shoji

  Frontiers Media S.A., 2021年05月, Frontiers in Microbiology, 12, 英語

  研究論文（学術雑誌）


• Molecular epidemiology and genetic diversity of norovirus infection in children hospitalized with acute gastroenteritis in East Java, Indonesia in 2015-2019.

  Takako Utsumi, Maria Inge Lusida, Zayyin Dinana, Rury Mega Wahyuni, Soegeng Soegijanto, Soetjipto, Alpha Fardah Athiyyah, Subijanto Marto Sudarmo, Reza Gunadi Ranuh, Andy Darma, Juniastuti, Laura Navika Yamani, Yen Hai Doan, Hiroyuki Shimizu, Koji Ishii, Chieko Matsui, Lin Deng, Takayuki Abe, Kazuhiko Katayama, Ikuo Shoji

  Noroviruses are recognized as a leading cause of outbreaks and sporadic cases of acute gastroenteritis (AGE) among individuals of all ages worldwide, especially in children <5 years old. We investigated the epidemiology of noroviruses among hospitalized children at two hospitals in East Java, Indonesia. Stool samples were collected from 966 children with AGE during September 2015-July 2019. All samples were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) for the amplification of both the RNA-dependent RNA polymerase (RdRp) and the capsid genes of noroviruses. The genotypes were determined by phylogenetic analyses. In 2015-2019, noroviruses were detected in 12.3% (119/966) of the samples. Children <2 years old showed a significantly higher prevalence than those ≥2 years old (P = 0.01). NoV infections were observed throughout the year, with the highest prevalence in December. Based on our genetic analyses of RdRp, GII.[P31] (43.7%, 31/71) was the most prevalent RdRp genotype, followed by GII.[P16] (36.6%, 26/71). GII.[P31] was a dominant genotype in 2016 and 2018, whereas GII.[P16] was a dominant genotype in 2015 and 2017. Among the capsid genotypes, the most predominant norovirus genotype from 2015 to 2018 was GII.4 Sydney_2012 (33.6%, 40/119). The most prevalent genotype in each year was GII.13 in 2015, GII.4 Sydney_2012 in 2016 and 2018, and GII.3 in 2017. Based on the genetic analyses of RdRp and capsid sequences, the strains were clustered into 13 RdRp/capsid genotypes; 12 of them were discordant, e.g., GII.4 Sydney[P31], GII.3[P16], and GII.13[P16]. The predominant genotype in each year was GII.13[P16] in 2015, GII.4 Sydney[P31] in 2016, GII.3[P16] in 2017, and GII.4 Sydney[P31] in 2018. Our results demonstrate high detection rates and genetic diversity of norovirus GII genotypes in pediatric AGE samples from Indonesia. These findings strengthen the importance of the continuous molecular surveillance of emerging norovirus strains.

  2021年03月, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 88, 104703 - 104703, 英語, 国際誌, 国際共著している

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

  Daniel J Klionsky, Amal Kamal Abdel-Aziz, Sara Abdelfatah, Mahmoud Abdellatif, Asghar Abdoli, Steffen Abel, Hagai Abeliovich, Marie H Abildgaard, Yakubu Princely Abudu, Abraham Acevedo-Arozena, Iannis E Adamopoulos, Khosrow Adeli, Timon E Adolph, Annagrazia Adornetto, Elma Aflaki, Galila Agam, Anupam Agarwal, Bharat B Aggarwal, Maria Agnello, Patrizia Agostinis, Javed N Agrewala, Alexander Agrotis, Patricia V Aguilar, S Tariq Ahmad, Zubair M Ahmed, Ulises Ahumada-Castro, Sonja Aits, Shu Aizawa, Yunus Akkoc, Tonia Akoumianaki, Hafize Aysin Akpinar, Ahmed M Al-Abd, Lina Al-Akra, Abeer Al-Gharaibeh, Moulay A Alaoui-Jamali, Simon Alberti, Elísabet Alcocer-Gómez, Cristiano Alessandri, Muhammad Ali, M Abdul Alim Al-Bari, Saeb Aliwaini, Javad Alizadeh, Eugènia Almacellas, Alexandru Almasan, Alicia Alonso, Guillermo D Alonso, Nihal Altan-Bonnet, Dario C Altieri, Élida M C Álvarez, Sara Alves, Cristine Alves da Costa, Mazen M Alzaharna, Marialaura Amadio, Consuelo Amantini, Cristina Amaral, Susanna Ambrosio, Amal O Amer, Veena Ammanathan, Zhenyi An, Stig U Andersen, Shaida A Andrabi, Magaiver Andrade-Silva, Allen M Andres, Sabrina Angelini, David Ann, Uche C Anozie, Mohammad Y Ansari, Pedro Antas, Adam Antebi, Zuriñe Antón, Tahira Anwar, Lionel Apetoh, Nadezda Apostolova, Toshiyuki Araki, Yasuhiro Araki, Kohei Arasaki, Wagner L Araújo, Jun Araya, Catherine Arden, Maria-Angeles Arévalo, Sandro Arguelles, Esperanza Arias, Jyothi Arikkath, Hirokazu Arimoto, Aileen R Ariosa, Darius Armstrong-James, Laetitia Arnauné-Pelloquin, Angeles Aroca, Daniela S Arroyo, Ivica Arsov, Rubén Artero, Dalia Maria Lucia Asaro, Michael Aschner, Milad Ashrafizadeh, Osnat Ashur-Fabian, Atanas G Atanasov, Alicia K Au, Patrick Auberger, Holger W Auner, Laure Aurelian, Riccardo Autelli, Laura Avagliano, Yenniffer Ávalos, Sanja Aveic, Célia Alexandra Aveleira, Tamar Avin-Wittenberg, Yucel Aydin, Scott Ayton, Srinivas Ayyadevara, Maria Azzopardi, Misuzu Baba, Jonathan M Backer, Steven K Backues, Dong-Hun Bae, Ok-Nam Bae, Soo Han Bae, Eric H Baehrecke, Ahruem Baek, Seung-Hoon Baek, Sung Hee Baek, Giacinto Bagetta, Agnieszka Bagniewska-Zadworna, Hua Bai, Jie Bai, Xiyuan Bai, Yidong Bai, Nandadulal Bairagi, Shounak Baksi, Teresa Balbi, Cosima T Baldari, Walter Balduini, Andrea Ballabio, Maria Ballester, Salma Balazadeh, Rena Balzan, Rina Bandopadhyay, Sreeparna Banerjee, Sulagna Banerjee, Ágnes Bánréti, Yan Bao, Mauricio S Baptista, Alessandra Baracca, Cristiana Barbati, Ariadna Bargiela, Daniela Barilà, Peter G Barlow, Sami J Barmada, Esther Barreiro, George E Barreto, Jiri Bartek, Bonnie Bartel, Alberto Bartolome, Gaurav R Barve, Suresh H Basagoudanavar, Diane C Bassham, Robert C Bast Jr, Alakananda Basu, Henri Batoko, Isabella Batten, Etienne E Baulieu, Bradley L Baumgarner, Jagadeesh Bayry, Rupert Beale, Isabelle Beau, Florian Beaumatin, Luiz R G Bechara, George R Beck Jr, Michael F Beers, Jakob Begun, Christian Behrends, Georg M N Behrens, Roberto Bei, Eloy Bejarano, Shai Bel, Christian Behl, Amine Belaid, Naïma Belgareh-Touzé, Cristina Bellarosa, Francesca Belleudi, Melissa Belló Pérez, Raquel Bello-Morales, Jackeline Soares de Oliveira Beltran, Sebastián Beltran, Doris Mangiaracina Benbrook, Mykolas Bendorius, Bruno A Benitez, Irene Benito-Cuesta, Julien Bensalem, Martin W Berchtold, Sabina Berezowska, Daniele Bergamaschi, Matteo Bergami, Andreas Bergmann, Laura Berliocchi, Clarisse Berlioz-Torrent, Amélie Bernard, Lionel Berthoux, Cagri G Besirli, Sebastien Besteiro, Virginie M Betin, Rudi Beyaert, Jelena S Bezbradica, Kiran Bhaskar, Ingrid Bhatia-Kissova, Resham Bhattacharya, Sujoy Bhattacharya, Shalmoli Bhattacharyya, Md Shenuarin Bhuiyan, Sujit Kumar Bhutia, Lanrong Bi, Xiaolin Bi, Trevor J Biden, Krikor Bijian, Viktor A Billes, Nadine Binart, Claudia Bincoletto, Asa B Birgisdottir, Geir Bjorkoy, Gonzalo Blanco, Ana Blas-Garcia, Janusz Blasiak, Robert Blomgran, Klas Blomgren, Janice S Blum, Emilio Boada-Romero, Mirta Boban, Kathleen Boesze-Battaglia, Philippe Boeuf, Barry Boland, Pascale Bomont, Paolo Bonaldo, Srinivasa Reddy Bonam, Laura Bonfili, Juan S Bonifacino, Brian A Boone, Martin D Bootman, Matteo Bordi, Christoph Borner, Beat C Bornhauser, Gautam Borthakur, Jürgen Bosch, Santanu Bose, Luis M Botana, Juan Botas, Chantal M Boulanger, Michael E Boulton, Mathieu Bourdenx, Benjamin Bourgeois, Nollaig M Bourke, Guilhem Bousquet, Patricia Boya, Peter V Bozhkov, Luiz H M Bozi, Tolga O Bozkurt, Doug E Brackney, Christian H Brandts, Ralf J Braun, Gerhard H Braus, Roberto Bravo-Sagua, José M Bravo-San Pedro, Patrick Brest, Marie-Agnès Bringer, Alfredo Briones-Herrera, V Courtney Broaddus, Peter Brodersen, Jeffrey L Brodsky, Steven L Brody, Paola G Bronson, Jeff M Bronstein, Carolyn N Brown, Rhoderick E Brown, Patricia C Brum, John H Brumell, Nicola Brunetti-Pierri, Daniele Bruno, Robert J Bryson-Richardson, Cecilia Bucci, Carmen Buchrieser, Marta Bueno, Laura Elisa Buitrago-Molina, Simone Buraschi, Shilpa Buch, J Ross Buchan, Erin M Buckingham, Hikmet Budak, Mauricio Budini, Geert Bultynck, Florin Burada, Joseph R Burgoyne, M Isabel Burón, Victor Bustos, Sabrina Büttner, Elena Butturini, Aaron Byrd, Isabel Cabas, Sandra Cabrera-Benitez, Ken Cadwell, Jingjing Cai, Lu Cai, Qian Cai, Montserrat Cairó, Jose A Calbet, Guy A Caldwell, Kim A Caldwell, Jarrod A Call, Riccardo Calvani, Ana C Calvo, Miguel Calvo-Rubio Barrera, Niels Os Camara, Jacques H Camonis, Nadine Camougrand, Michelangelo Campanella, Edward M Campbell, François-Xavier Campbell-Valois, Silvia Campello, Ilaria Campesi, Juliane C Campos, Olivier Camuzard, Jorge Cancino, Danilo Candido de Almeida, Laura Canesi, Isabella Caniggia, Barbara Canonico, Carles Cantí, Bin Cao, Michele Caraglia, Beatriz Caramés, Evie H Carchman, Elena Cardenal-Muñoz, Cesar Cardenas, Luis Cardenas, Sandra M Cardoso, Jennifer S Carew, Georges F Carle, Gillian Carleton, Silvia Carloni, Didac Carmona-Gutierrez, Leticia A Carneiro, Oliana Carnevali, Julian M Carosi, Serena Carra, Alice Carrier, Lucie Carrier, Bernadette Carroll, A Brent Carter, Andreia Neves Carvalho, Magali Casanova, Caty Casas, Josefina Casas, Chiara Cassioli, Eliseo F Castillo, Karen Castillo, Sonia Castillo-Lluva, Francesca Castoldi, Marco Castori, Ariel F Castro, Margarida Castro-Caldas, Javier Castro-Hernandez, Susana Castro-Obregon, Sergio D Catz, Claudia Cavadas, Federica Cavaliere, Gabriella Cavallini, Maria Cavinato, Maria L Cayuela, Paula Cebollada Rica, Valentina Cecarini, Francesco Cecconi, Marzanna Cechowska-Pasko, Simone Cenci, Victòria Ceperuelo-Mallafré, João J Cerqueira, Janete M Cerutti, Davide Cervia, Vildan Bozok Cetintas, Silvia Cetrullo, Han-Jung Chae, Andrei S Chagin, Chee-Yin Chai, Gopal Chakrabarti, Oishee Chakrabarti, Tapas Chakraborty, Trinad Chakraborty, Mounia Chami, Georgios Chamilos, David W Chan, Edmond Y W Chan, Edward D Chan, H Y Edwin Chan, Helen H Chan, Hung Chan, Matthew T V Chan, Yau Sang Chan, Partha K Chandra, Chih-Peng Chang, Chunmei Chang, Hao-Chun Chang, Kai Chang, Jie Chao, Tracey Chapman, Nicolas Charlet-Berguerand, Samrat Chatterjee, Shail K Chaube, Anu Chaudhary, Santosh Chauhan, Edward Chaum, Frédéric Checler, Michael E Cheetham, Chang-Shi Chen, Guang-Chao Chen, Jian-Fu Chen, Liam L Chen, Leilei Chen, Lin Chen, Mingliang Chen, Mu-Kuan Chen, Ning Chen, Quan Chen, Ruey-Hwa Chen, Shi Chen, Wei Chen, Weiqiang Chen, Xin-Ming Chen, Xiong-Wen Chen, Xu Chen, Yan Chen, Ye-Guang Chen, Yingyu Chen, Yongqiang Chen, Yu-Jen Chen, Yue-Qin Chen, Zhefan Stephen Chen, Zhi Chen, Zhi-Hua Chen, Zhijian J Chen, Zhixiang Chen, Hanhua Cheng, Jun Cheng, Shi-Yuan Cheng, Wei Cheng, Xiaodong Cheng, Xiu-Tang Cheng, Yiyun Cheng, Zhiyong Cheng, Zhong Chen, Heesun Cheong, Jit Kong Cheong, Boris V Chernyak, Sara Cherry, Chi Fai Randy Cheung, Chun Hei Antonio Cheung, King-Ho Cheung, Eric Chevet, Richard J Chi, Alan Kwok Shing Chiang, Ferdinando Chiaradonna, Roberto Chiarelli, Mario Chiariello, Nathalia Chica, Susanna Chiocca, Mario Chiong, Shih-Hwa Chiou, Abhilash I Chiramel, Valerio Chiurchiù, Dong-Hyung Cho, Seong-Kyu Choe, Augustine M K Choi, Mary E Choi, Kamalika Roy Choudhury, Norman S Chow, Charleen T Chu, Jason P Chua, John Jia En Chua, Hyewon Chung, Kin Pan Chung, Seockhoon Chung, So-Hyang Chung, Yuen-Li Chung, Valentina Cianfanelli, Iwona A Ciechomska, Mariana Cifuentes, Laura Cinque, Sebahattin Cirak, Mara Cirone, Michael J Clague, Robert Clarke, Emilio Clementi, Eliana M Coccia, Patrice Codogno, Ehud Cohen, Mickael M Cohen, Tania Colasanti, Fiorella Colasuonno, Robert A Colbert, Anna Colell, Miodrag Čolić, Nuria S Coll, Mark O Collins, María I Colombo, Daniel A Colón-Ramos, Lydie Combaret, Sergio Comincini, Márcia R Cominetti, Antonella Consiglio, Andrea Conte, Fabrizio Conti, Viorica Raluca Contu, Mark R Cookson, Kevin M Coombs, Isabelle Coppens, Maria Tiziana Corasaniti, Dale P Corkery, Nils Cordes, Katia Cortese, Maria do Carmo Costa, Sarah Costantino, Paola Costelli, Ana Coto-Montes, Peter J Crack, Jose L Crespo, Alfredo Criollo, Valeria Crippa, Riccardo Cristofani, Tamas Csizmadia, Antonio Cuadrado, Bing Cui, Jun Cui, Yixian Cui, Yong Cui, Emmanuel Culetto, Andrea C Cumino, Andrey V Cybulsky, Mark J Czaja, Stanislaw J Czuczwar, Stefania D'Adamo, Marcello D'Amelio, Daniela D'Arcangelo, Andrew C D'Lugos, Gabriella D'Orazi, James A da Silva, Hormos Salimi Dafsari, Ruben K Dagda, Yasin Dagdas, Maria Daglia, Xiaoxia Dai, Yun Dai, Yuyuan Dai, Jessica Dal Col, Paul Dalhaimer, Luisa Dalla Valle, Tobias Dallenga, Guillaume Dalmasso, Markus Damme, Ilaria Dando, Nico P Dantuma, April L Darling, Hiranmoy Das, Srinivasan Dasarathy, Santosh K Dasari, Srikanta Dash, Oliver Daumke, Adrian N Dauphinee, Jeffrey S Davies, Valeria A Dávila, Roger J Davis, Tanja Davis, Sharadha Dayalan Naidu, Francesca De Amicis, Karolien De Bosscher, Francesca De Felice, Lucia De Franceschi, Chiara De Leonibus, Mayara G de Mattos Barbosa, Guido R Y De Meyer, Angelo De Milito, Cosimo De Nunzio, Clara De Palma, Mauro De Santi, Claudio De Virgilio, Daniela De Zio, Jayanta Debnath, Brian J DeBosch, Jean-Paul Decuypere, Mark A Deehan, Gianluca Deflorian, James DeGregori, Benjamin Dehay, Gabriel Del Rio, Joe R Delaney, Lea M D Delbridge, Elizabeth Delorme-Axford, M Victoria Delpino, Francesca Demarchi, Vilma Dembitz, Nicholas D Demers, Hongbin Deng, Zhiqiang Deng, Joern Dengjel, Paul Dent, Donna Denton, Melvin L DePamphilis, Channing J Der, Vojo Deretic, Albert Descoteaux, Laura Devis, Sushil Devkota, Olivier Devuyst, Grant Dewson, Mahendiran Dharmasivam, Rohan Dhiman, Diego di Bernardo, Manlio Di Cristina, Fabio Di Domenico, Pietro Di Fazio, Alessio Di Fonzo, Giovanni Di Guardo, Gianni M Di Guglielmo, Luca Di Leo, Chiara Di Malta, Alessia Di Nardo, Martina Di Rienzo, Federica Di Sano, George Diallinas, Jiajie Diao, Guillermo Diaz-Araya, Inés Díaz-Laviada, Jared M Dickinson, Marc Diederich, Mélanie Dieudé, Ivan Dikic, Shiping Ding, Wen-Xing Ding, Luciana Dini, Jelena Dinić, Miroslav Dinic, Albena T Dinkova-Kostova, Marc S Dionne, Jörg H W Distler, Abhinav Diwan, Ian M C Dixon, Mojgan Djavaheri-Mergny, Ina Dobrinski, Oxana Dobrovinskaya, Radek Dobrowolski, Renwick C J Dobson, Jelena Đokić, Serap Dokmeci Emre, Massimo Donadelli, Bo Dong, Xiaonan Dong, Zhiwu Dong, Gerald W Dorn Ii, Volker Dotsch, Huan Dou, Juan Dou, Moataz Dowaidar, Sami Dridi, Liat Drucker, Ailian Du, Caigan Du, Guangwei Du, Hai-Ning Du, Li-Lin Du, André du Toit, Shao-Bin Duan, Xiaoqiong Duan, Sónia P Duarte, Anna Dubrovska, Elaine A Dunlop, Nicolas Dupont, Raúl V Durán, Bilikere S Dwarakanath, Sergey A Dyshlovoy, Darius Ebrahimi-Fakhari, Leopold Eckhart, Charles L Edelstein, Thomas Efferth, Eftekhar Eftekharpour, Ludwig Eichinger, Nabil Eid, Tobias Eisenberg, N Tony Eissa, Sanaa Eissa, Miriam Ejarque, Abdeljabar El Andaloussi, Nazira El-Hage, Shahenda El-Naggar, Anna Maria Eleuteri, Eman S El-Shafey, Mohamed Elgendy, Aristides G Eliopoulos, María M Elizalde, Philip M Elks, Hans-Peter Elsasser, Eslam S Elsherbiny, Brooke M Emerling, N C Tolga Emre, Christina H Eng, Nikolai Engedal, Anna-Mart Engelbrecht, Agnete S T Engelsen, Jorrit M Enserink, Ricardo Escalante, Audrey Esclatine, Mafalda Escobar-Henriques, Eeva-Liisa Eskelinen, Lucile Espert, Makandjou-Ola Eusebio, Gemma Fabrias, Cinzia Fabrizi, Antonio Facchiano, Francesco Facchiano, Bengt Fadeel, Claudio Fader, Alex C Faesen, W Douglas Fairlie, Alberto Falcó, Bjorn H Falkenburger, Daping Fan, Jie Fan, Yanbo Fan, Evandro F Fang, Yanshan Fang, Yognqi Fang, Manolis Fanto, Tamar Farfel-Becker, Mathias Faure, Gholamreza Fazeli, Anthony O Fedele, Arthur M Feldman, Du Feng, Jiachun Feng, Lifeng Feng, Yibin Feng, Yuchen Feng, Wei Feng, Thais Fenz Araujo, Thomas A Ferguson, Álvaro F Fernández, Jose C Fernandez-Checa, Sonia Fernández-Veledo, Alisdair R Fernie, Anthony W Ferrante Jr, Alessandra Ferraresi, Merari F Ferrari, Julio C B Ferreira, Susan Ferro-Novick, Antonio Figueras, Riccardo Filadi, Nicoletta Filigheddu, Eduardo Filippi-Chiela, Giuseppe Filomeni, Gian Maria Fimia, Vittorio Fineschi, Francesca Finetti, Steven Finkbeiner, Edward A Fisher, Paul B Fisher, Flavio Flamigni, Steven J Fliesler, Trude H Flo, Ida Florance, Oliver Florey, Tullio Florio, Erika Fodor, Carlo Follo, Edward A Fon, Antonella Forlino, Francesco Fornai, Paola Fortini, Anna Fracassi, Alessandro Fraldi, Brunella Franco, Rodrigo Franco, Flavia Franconi, Lisa B Frankel, Scott L Friedman, Leopold F Fröhlich, Gema Frühbeck, Jose M Fuentes, Yukio Fujiki, Naonobu Fujita, Yuuki Fujiwara, Mitsunori Fukuda, Simone Fulda, Luc Furic, Norihiko Furuya, Carmela Fusco, Michaela U Gack, Lidia Gaffke, Sehamuddin Galadari, Alessia Galasso, Maria F Galindo, Sachith Gallolu Kankanamalage, Lorenzo Galluzzi, Vincent Galy, Noor Gammoh, Boyi Gan, Ian G Ganley, Feng Gao, Hui Gao, Minghui Gao, Ping Gao, Shou-Jiang Gao, Wentao Gao, Xiaobo Gao, Ana Garcera, Maria Noé Garcia, Verónica E Garcia, Francisco García-Del Portillo, Vega Garcia-Escudero, Aracely Garcia-Garcia, Marina Garcia-Macia, Diana García-Moreno, Carmen Garcia-Ruiz, Patricia García-Sanz, Abhishek D Garg, Ricardo Gargini, Tina Garofalo, Robert F Garry, Nils C Gassen, Damian Gatica, Liang Ge, Wanzhong Ge, Ruth Geiss-Friedlander, Cecilia Gelfi, Pascal Genschik, Ian E Gentle, Valeria Gerbino, Christoph Gerhardt, Kyla Germain, Marc Germain, David A Gewirtz, Elham Ghasemipour Afshar, Saeid Ghavami, Alessandra Ghigo, Manosij Ghosh, Georgios Giamas, Claudia Giampietri, Alexandra Giatromanolaki, Gary E Gibson, Spencer B Gibson, Vanessa Ginet, Edward Giniger, Carlotta Giorgi, Henrique Girao, Stephen E Girardin, Mridhula Giridharan, Sandy Giuliano, Cecilia Giulivi, Sylvie Giuriato, Julien Giustiniani, Alexander Gluschko, Veit Goder, Alexander Goginashvili, Jakub Golab, David C Goldstone, Anna Golebiewska, Luciana R Gomes, Rodrigo Gomez, Rubén Gómez-Sánchez, Maria Catalina Gomez-Puerto, Raquel Gomez-Sintes, Qingqiu Gong, Felix M Goni, Javier González-Gallego, Tomas Gonzalez-Hernandez, Rosa A Gonzalez-Polo, Jose A Gonzalez-Reyes, Patricia González-Rodríguez, Ing Swie Goping, Marina S Gorbatyuk, Nikolai V Gorbunov, Kıvanç Görgülü, Roxana M Gorojod, Sharon M Gorski, Sandro Goruppi, Cecilia Gotor, Roberta A Gottlieb, Illana Gozes, Devrim Gozuacik, Martin Graef, Markus H Gräler, Veronica Granatiero, Daniel Grasso, Joshua P Gray, Douglas R Green, Alexander Greenhough, Stephen L Gregory, Edward F Griffin, Mark W Grinstaff, Frederic Gros, Charles Grose, Angelina S Gross, Florian Gruber, Paolo Grumati, Tilman Grune, Xueyan Gu, Jun-Lin Guan, Carlos M Guardia, Kishore Guda, Flora Guerra, Consuelo Guerri, Prasun Guha, Carlos Guillén, Shashi Gujar, Anna Gukovskaya, Ilya Gukovsky, Jan Gunst, Andreas Günther, Anyonya R Guntur, Chuanyong Guo, Chun Guo, Hongqing Guo, Lian-Wang Guo, Ming Guo, Pawan Gupta, Shashi Kumar Gupta, Swapnil Gupta, Veer Bala Gupta, Vivek Gupta, Asa B Gustafsson, David D Gutterman, Ranjitha H B, Annakaisa Haapasalo, James E Haber, Aleksandra Hać, Shinji Hadano, Anders J Hafrén, Mansour Haidar, Belinda S Hall, Gunnel Halldén, Anne Hamacher-Brady, Andrea Hamann, Maho Hamasaki, Weidong Han, Malene Hansen, Phyllis I Hanson, Zijian Hao, Masaru Harada, Ljubica Harhaji-Trajkovic, Nirmala Hariharan, Nigil Haroon, James Harris, Takafumi Hasegawa, Noor Hasima Nagoor, Jeffrey A Haspel, Volker Haucke, Wayne D Hawkins, Bruce A Hay, Cole M Haynes, Soren B Hayrabedyan, Thomas S Hays, Congcong He, Qin He, Rong-Rong He, You-Wen He, Yu-Ying He, Yasser Heakal, Alexander M Heberle, J Fielding Hejtmancik, Gudmundur Vignir Helgason, Vanessa Henkel, Marc Herb, Alexander Hergovich, Anna Herman-Antosiewicz, Agustín Hernández, Carlos Hernandez, Sergio Hernandez-Diaz, Virginia Hernandez-Gea, Amaury Herpin, Judit Herreros, Javier H Hervás, Daniel Hesselson, Claudio Hetz, Volker T Heussler, Yujiro Higuchi, Sabine Hilfiker, Joseph A Hill, William S Hlavacek, Emmanuel A Ho, Idy H T Ho, Philip Wing-Lok Ho, Shu-Leong Ho, Wan Yun Ho, G Aaron Hobbs, Mark Hochstrasser, Peter H 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Rodriguez-Henche, Humberto Rodriguez-Rocha, Jeroen Roelofs, Robert S Rogers, Vladimir V Rogov, Ana I Rojo, Krzysztof Rolka, Vanina Romanello, Luigina Romani, Alessandra Romano, Patricia S Romano, David Romeo-Guitart, Luis C Romero, Montserrat Romero, Joseph C Roney, Christopher Rongo, Sante Roperto, Mathias T Rosenfeldt, Philip Rosenstiel, Anne G Rosenwald, Kevin A Roth, Lynn Roth, Steven Roth, Kasper M A Rouschop, Benoit D Roussel, Sophie Roux, Patrizia Rovere-Querini, Ajit Roy, Aurore Rozieres, Diego Ruano, David C Rubinsztein, Maria P Rubtsova, Klaus Ruckdeschel, Christoph Ruckenstuhl, Emil Rudolf, Rüdiger Rudolf, Alessandra Ruggieri, Avnika Ashok Ruparelia, Paola Rusmini, Ryan R Russell, Gian Luigi Russo, Maria Russo, Rossella Russo, Oxana O Ryabaya, Kevin M Ryan, Kwon-Yul Ryu, Maria Sabater-Arcis, Ulka Sachdev, Michael Sacher, Carsten Sachse, Abhishek Sadhu, Junichi Sadoshima, Nathaniel Safren, Paul Saftig, Antonia P Sagona, Gaurav Sahay, Amirhossein Sahebkar, Mustafa Sahin, Ozgur Sahin, Sumit Sahni, Nayuta Saito, Shigeru Saito, Tsunenori Saito, Ryohei Sakai, Yasuyoshi Sakai, Jun-Ichi Sakamaki, Kalle Saksela, Gloria Salazar, Anna Salazar-Degracia, Ghasem H Salekdeh, Ashok K Saluja, Belém Sampaio-Marques, Maria Cecilia Sanchez, Jose A Sanchez-Alcazar, Victoria Sanchez-Vera, Vanessa Sancho-Shimizu, J Thomas Sanderson, Marco Sandri, Stefano Santaguida, Laura Santambrogio, Magda M Santana, Giorgio Santoni, Alberto Sanz, Pascual Sanz, Shweta Saran, Marco Sardiello, Timothy J Sargeant, Apurva Sarin, Chinmoy Sarkar, Sovan Sarkar, Maria-Rosa Sarrias, Surajit Sarkar, Dipanka Tanu Sarmah, Jaakko Sarparanta, Aishwarya Sathyanarayan, Ranganayaki Sathyanarayanan, K Matthew Scaglione, Francesca Scatozza, Liliana Schaefer, Zachary T Schafer, Ulrich E Schaible, Anthony H V Schapira, Michael Scharl, Hermann M Schatzl, Catherine H Schein, Wiep Scheper, David Scheuring, Maria Vittoria Schiaffino, Monica Schiappacassi, Rainer Schindl, Uwe Schlattner, Oliver Schmidt, Roland Schmitt, Stephen D Schmidt, Ingo Schmitz, Eran Schmukler, Anja Schneider, Bianca E Schneider, Romana Schober, Alejandra C Schoijet, Micah B Schott, Michael Schramm, Bernd Schröder, Kai Schuh, Christoph Schüller, Ryan J Schulze, Lea Schürmanns, Jens C Schwamborn, Melanie Schwarten, Filippo Scialo, Sebastiano Sciarretta, Melanie J Scott, Kathleen W Scotto, A Ivana Scovassi, Andrea Scrima, Aurora Scrivo, David Sebastian, Salwa Sebti, Simon Sedej, Laura Segatori, Nava Segev, Per O Seglen, Iban Seiliez, Ekihiro Seki, Scott B Selleck, Frank W Sellke, Joshua T Selsby, Michael Sendtner, Serif Senturk, Elena Seranova, Consolato Sergi, Ruth Serra-Moreno, Hiromi Sesaki, Carmine Settembre, Subba Rao Gangi Setty, Gianluca Sgarbi, Ou Sha, John J Shacka, Javeed A Shah, Dantong Shang, Changshun Shao, Feng Shao, Soroush Sharbati, Lisa M Sharkey, Dipali Sharma, Gaurav Sharma, Kulbhushan Sharma, Pawan Sharma, Surendra Sharma, Han-Ming Shen, Hongtao Shen, Jiangang Shen, Ming Shen, Weili Shen, Zheni Shen, Rui Sheng, Zhi Sheng, Zu-Hang Sheng, Jianjian Shi, Xiaobing Shi, Ying-Hong Shi, Kahori Shiba-Fukushima, Jeng-Jer Shieh, Yohta Shimada, Shigeomi Shimizu, Makoto Shimozawa, Takahiro Shintani, Christopher J Shoemaker, Shahla Shojaei, Ikuo Shoji, Bhupendra V Shravage, Viji Shridhar, Chih-Wen Shu, Hong-Bing Shu, Ke Shui, Arvind K Shukla, Timothy E Shutt, Valentina Sica, Aleem Siddiqui, Amanda Sierra, Virginia Sierra-Torre, Santiago Signorelli, Payel Sil, Bruno J de Andrade Silva, Johnatas D Silva, Eduardo Silva-Pavez, Sandrine Silvente-Poirot, Rachel E Simmonds, Anna Katharina Simon, Hans-Uwe Simon, Matias Simons, Anurag Singh, Lalit P Singh, Rajat Singh, Shivendra V Singh, Shrawan K Singh, Sudha B Singh, Sunaina Singh, Surinder Pal Singh, Debasish Sinha, Rohit Anthony Sinha, Sangita Sinha, Agnieszka Sirko, Kapil Sirohi, Efthimios L Sivridis, Panagiotis Skendros, Aleksandra Skirycz, Iva Slaninová, Soraya S Smaili, Andrei Smertenko, Matthew D Smith, Stefaan J Soenen, Eun Jung Sohn, Sophia P M Sok, Giancarlo Solaini, Thierry Soldati, Scott A Soleimanpour, Rosa M Soler, Alexei Solovchenko, Jason A Somarelli, Avinash Sonawane, Fuyong Song, Hyun Kyu Song, Ju-Xian Song, Kunhua Song, Zhiyin Song, Leandro R Soria, Maurizio Sorice, Alexander A Soukas, Sandra-Fausia Soukup, Diana Sousa, Nadia Sousa, Paul A Spagnuolo, Stephen A Spector, M M Srinivas Bharath, Daret St Clair, Venturina Stagni, Leopoldo Staiano, Clint A Stalnecker, Metodi V Stankov, Peter B Stathopulos, Katja Stefan, Sven Marcel Stefan, Leonidas Stefanis, Joan S Steffan, Alexander Steinkasserer, Harald Stenmark, Jared Sterneckert, Craig Stevens, Veronika Stoka, Stephan Storch, Björn Stork, Flavie Strappazzon, Anne Marie Strohecker, Dwayne G Stupack, Huanxing Su, Ling-Yan Su, Longxiang Su, Ana M Suarez-Fontes, Carlos S Subauste, Selvakumar Subbian, Paula V Subirada, Ganapasam Sudhandiran, Carolyn M Sue, Xinbing Sui, Corey Summers, Guangchao Sun, Jun Sun, Kang Sun, Meng-Xiang Sun, Qiming Sun, Yi Sun, Zhongjie Sun, Karen K S Sunahara, Eva Sundberg, Katalin Susztak, Peter Sutovsky, Hidekazu Suzuki, Gary Sweeney, J David Symons, Stephen Cho Wing Sze, Nathaniel J Szewczyk, Anna Tabęcka-Łonczynska, Claudio Tabolacci, Frank Tacke, Heinrich Taegtmeyer, Marco Tafani, Mitsuo Tagaya, Haoran Tai, Stephen W G Tait, Yoshinori Takahashi, Szabolcs Takats, Priti Talwar, Chit Tam, Shing Yau Tam, Davide Tampellini, Atsushi Tamura, Chong Teik Tan, Eng-King Tan, Ya-Qin Tan, Masaki Tanaka, Motomasa Tanaka, Daolin Tang, Jingfeng Tang, Tie-Shan Tang, Isei Tanida, Zhipeng Tao, Mohammed Taouis, Lars Tatenhorst, Nektarios Tavernarakis, Allen Taylor, Gregory A Taylor, Joan M Taylor, Elena Tchetina, Andrew R Tee, Irmgard Tegeder, David Teis, Natercia Teixeira, Fatima Teixeira-Clerc, Kumsal A Tekirdag, Tewin Tencomnao, Sandra Tenreiro, Alexei V Tepikin, Pilar S Testillano, Gianluca Tettamanti, Pierre-Louis Tharaux, Kathrin Thedieck, Arvind A Thekkinghat, Stefano Thellung, Josephine W Thinwa, V P Thirumalaikumar, Sufi Mary Thomas, Paul G Thomes, Andrew Thorburn, Lipi Thukral, Thomas Thum, Michael Thumm, Ling Tian, Ales Tichy, Andreas Till, Vincent Timmerman, Vladimir I Titorenko, Sokol V Todi, Krassimira Todorova, Janne M Toivonen, Luana Tomaipitinca, Dhanendra Tomar, Cristina Tomas-Zapico, Sergej Tomić, Benjamin Chun-Kit Tong, Chao Tong, Xin Tong, Sharon A Tooze, Maria L Torgersen, Satoru Torii, Liliana Torres-López, Alicia Torriglia, Christina G Towers, Roberto Towns, Shinya Toyokuni, Vladimir Trajkovic, Donatella Tramontano, Quynh-Giao Tran, Leonardo H Travassos, Charles B Trelford, Shirley Tremel, Ioannis P Trougakos, Betty P Tsao, Mario P Tschan, Hung-Fat Tse, Tak Fu Tse, Hitoshi Tsugawa, Andrey S Tsvetkov, David A Tumbarello, Yasin Tumtas, María J Tuñón, Sandra Turcotte, Boris Turk, Vito Turk, Bradley J Turner, Richard I Tuxworth, Jessica K Tyler, Elena V Tyutereva, Yasuo Uchiyama, Aslihan Ugun-Klusek, Holm H Uhlig, Marzena Ułamek-Kozioł, Ilya V Ulasov, Midori Umekawa, Christian Ungermann, Rei Unno, Sylvie Urbe, Elisabet Uribe-Carretero, Suayib Üstün, Vladimir N Uversky, Thomas Vaccari, Maria I Vaccaro, Björn F Vahsen, Helin Vakifahmetoglu-Norberg, Rut Valdor, Maria J Valente, Ayelén Valko, Richard B Vallee, Angela M Valverde, Greet Van den Berghe, Stijn van der Veen, Luc Van Kaer, Jorg van Loosdregt, Sjoerd J L van Wijk, Wim Vandenberghe, Ilse Vanhorebeek, Marcos A Vannier-Santos, Nicola Vannini, M Cristina Vanrell, Chiara Vantaggiato, Gabriele Varano, Isabel Varela-Nieto, Máté Varga, M Helena Vasconcelos, Somya Vats, Demetrios G Vavvas, Ignacio Vega-Naredo, Silvia Vega-Rubin-de-Celis, Guillermo Velasco, Ariadna P Velázquez, Tibor Vellai, Edo Vellenga, Francesca Velotti, Mireille Verdier, Panayotis Verginis, Isabelle Vergne, Paul Verkade, Manish Verma, Patrik Verstreken, Tim Vervliet, Jörg Vervoorts, Alexandre T Vessoni, Victor M Victor, Michel Vidal, Chiara Vidoni, Otilia V Vieira, Richard D Vierstra, Sonia Viganó, Helena Vihinen, Vinoy Vijayan, Miquel Vila, Marçal Vilar, José M Villalba, Antonio Villalobo, Beatriz Villarejo-Zori, Francesc Villarroya, Joan Villarroya, Olivier Vincent, Cecile Vindis, Christophe Viret, Maria Teresa Viscomi, Dora Visnjic, Ilio Vitale, David J Vocadlo, Olga V Voitsekhovskaja, Cinzia Volonté, Mattia Volta, Marta Vomero, Clarissa Von Haefen, Marc A Vooijs, Wolfgang Voos, Ljubica Vucicevic, Richard Wade-Martins, Satoshi Waguri, Kenrick A Waite, Shuji Wakatsuki, David W Walker, Mark J Walker, Simon A Walker, Jochen Walter, Francisco G Wandosell, Bo Wang, Chao-Yung Wang, Chen Wang, Chenran Wang, Chenwei Wang, Cun-Yu Wang, Dong Wang, Fangyang Wang, Feng Wang, Fengming Wang, Guansong Wang, Han Wang, Hao Wang, Hexiang Wang, Hong-Gang Wang, Jianrong Wang, Jigang Wang, Jiou Wang, Jundong Wang, Kui Wang, Lianrong Wang, Liming Wang, Maggie Haitian Wang, Meiqing Wang, Nanbu Wang, Pengwei Wang, Peipei Wang, Ping Wang, Ping Wang, Qing Jun Wang, Qing Wang, Qing Kenneth Wang, Qiong A Wang, Wen-Tao Wang, Wuyang Wang, Xinnan Wang, Xuejun Wang, Yan Wang, Yanchang Wang, Yanzhuang Wang, Yen-Yun Wang, Yihua Wang, Yipeng Wang, Yu Wang, Yuqi Wang, Zhe Wang, Zhenyu Wang, Zhouguang Wang, Gary Warnes, Verena Warnsmann, Hirotaka Watada, Eizo Watanabe, Maxinne Watchon, Anna Wawrzyńska, Timothy E Weaver, Grzegorz Wegrzyn, Ann M Wehman, Huafeng Wei, Lei Wei, Taotao Wei, Yongjie Wei, Oliver H Weiergräber, Conrad C Weihl, Günther Weindl, Ralf Weiskirchen, Alan Wells, Runxia H Wen, Xin Wen, Antonia Werner, Beatrice Weykopf, Sally P Wheatley, J Lindsay Whitton, Alexander J Whitworth, Katarzyna Wiktorska, Manon E Wildenberg, Tom Wileman, Simon Wilkinson, Dieter Willbold, Brett Williams, Robin S B Williams, Roger L Williams, Peter R Williamson, Richard A Wilson, Beate Winner, Nathaniel J Winsor, Steven S Witkin, Harald Wodrich, Ute Woehlbier, Thomas Wollert, Esther Wong, Jack Ho Wong, Richard W Wong, Vincent Kam Wai Wong, W Wei-Lynn Wong, An-Guo Wu, Chengbiao Wu, Jian Wu, Junfang Wu, Kenneth K Wu, Min Wu, Shan-Ying Wu, Shengzhou Wu, Shu-Yan Wu, Shufang Wu, William K K Wu, Xiaohong Wu, Xiaoqing Wu, Yao-Wen Wu, Yihua Wu, Ramnik J Xavier, Hongguang Xia, Lixin Xia, Zhengyuan Xia, Ge Xiang, Jin Xiang, Mingliang Xiang, Wei Xiang, Bin Xiao, Guozhi Xiao, Hengyi Xiao, Hong-Tao Xiao, Jian Xiao, Lan Xiao, Shi Xiao, Yin Xiao, Baoming Xie, Chuan-Ming Xie, Min Xie, Yuxiang Xie, Zhiping Xie, Zhonglin Xie, Maria Xilouri, Congfeng Xu, En Xu, Haoxing Xu, Jing Xu, JinRong Xu, Liang Xu, Wen Wen Xu, Xiulong Xu, Yu Xue, Sokhna M S Yakhine-Diop, Masamitsu Yamaguchi, Osamu Yamaguchi, Ai Yamamoto, Shunhei Yamashina, Shengmin Yan, Shian-Jang Yan, Zhen Yan, Yasuo Yanagi, Chuanbin Yang, Dun-Sheng Yang, Huan Yang, Huang-Tian Yang, Hui Yang, Jin-Ming Yang, Jing Yang, Jingyu Yang, Ling Yang, Liu Yang, Ming Yang, Pei-Ming Yang, Qian Yang, Seungwon Yang, Shu Yang, Shun-Fa Yang, Wannian Yang, Wei Yuan Yang, Xiaoyong Yang, Xuesong Yang, Yi Yang, Ying Yang, Honghong Yao, Shenggen Yao, Xiaoqiang Yao, Yong-Gang Yao, Yong-Ming Yao, Takahiro Yasui, Meysam Yazdankhah, Paul M Yen, Cong Yi, Xiao-Ming Yin, Yanhai Yin, Zhangyuan Yin, Ziyi Yin, Meidan Ying, Zheng Ying, Calvin K Yip, Stephanie Pei Tung Yiu, Young H Yoo, Kiyotsugu Yoshida, Saori R Yoshii, Tamotsu Yoshimori, Bahman Yousefi, Boxuan Yu, Haiyang Yu, Jun Yu, Jun Yu, Li Yu, Ming-Lung Yu, Seong-Woon Yu, Victor C Yu, W Haung Yu, Zhengping Yu, Zhou Yu, Junying Yuan, Ling-Qing Yuan, Shilin Yuan, Shyng-Shiou F Yuan, Yanggang Yuan, Zengqiang Yuan, Jianbo Yue, Zhenyu Yue, Jeanho Yun, Raymond L Yung, David N Zacks, Gabriele Zaffagnini, Vanessa O Zambelli, Isabella Zanella, Qun S Zang, Sara Zanivan, Silvia Zappavigna, Pilar Zaragoza, Konstantinos S Zarbalis, Amir Zarebkohan, Amira Zarrouk, Scott O Zeitlin, Jialiu Zeng, Ju-Deng Zeng, Eva Žerovnik, Lixuan Zhan, Bin Zhang, Donna D Zhang, Hanlin Zhang, Hong Zhang, Hong Zhang, Honghe Zhang, Huafeng Zhang, Huaye Zhang, Hui Zhang, Hui-Ling Zhang, Jianbin Zhang, Jianhua Zhang, Jing-Pu Zhang, Kalin Y B Zhang, Leshuai W Zhang, Lin Zhang, Lisheng Zhang, Lu Zhang, Luoying Zhang, Menghuan Zhang, Peng Zhang, Sheng Zhang, Wei Zhang, Xiangnan Zhang, Xiao-Wei Zhang, Xiaolei Zhang, Xiaoyan Zhang, Xin Zhang, Xinxin Zhang, Xu Dong Zhang, Yang Zhang, Yanjin Zhang, Yi Zhang, Ying-Dong Zhang, Yingmei Zhang, Yuan-Yuan Zhang, Yuchen Zhang, Zhe Zhang, Zhengguang Zhang, Zhibing Zhang, Zhihai Zhang, Zhiyong Zhang, Zili Zhang, Haobin Zhao, Lei Zhao, Shuang Zhao, Tongbiao Zhao, Xiao-Fan Zhao, Ying Zhao, Yongchao Zhao, Yongliang Zhao, Yuting Zhao, Guoping Zheng, Kai Zheng, Ling Zheng, Shizhong Zheng, Xi-Long Zheng, Yi Zheng, Zu-Guo Zheng, Boris Zhivotovsky, Qing Zhong, Ao Zhou, Ben Zhou, Cefan Zhou, Gang Zhou, Hao Zhou, Hong Zhou, Hongbo Zhou, Jie Zhou, Jing Zhou, Jing Zhou, Jiyong Zhou, Kailiang Zhou, Rongjia Zhou, Xu-Jie Zhou, Yanshuang Zhou, Yinghong Zhou, Yubin Zhou, Zheng-Yu Zhou, Zhou Zhou, Binglin Zhu, Changlian Zhu, Guo-Qing Zhu, Haining Zhu, Hongxin Zhu, Hua Zhu, Wei-Guo Zhu, Yanping Zhu, Yushan Zhu, Haixia Zhuang, Xiaohong Zhuang, Katarzyna Zientara-Rytter, Christine M Zimmermann, Elena Ziviani, Teresa Zoladek, Wei-Xing Zong, Dmitry B Zorov, Antonio Zorzano, Weiping Zou, Zhen Zou, Zhengzhi Zou, Steven Zuryn, Werner Zwerschke, Beate Brand-Saberi, X Charlie Dong, Chandra Shekar Kenchappa, Zuguo Li, Yong Lin, Shigeru Oshima, Yueguang Rong, Judith C Sluimer, Christina L Stallings, Chun-Kit Tong

  In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

  2021年02月, Autophagy, 17(1) (1), 1 - 382, 英語, 国際誌, 国際共著している

  [査読有り]

  研究論文（学術雑誌）


• The Role of Chaperone-Mediated Autophagy in Hepatitis C Virus-Induced Pathogenesis.

  Chieko Matsui, Putu Yuliandari, Lin Deng, Takayuki Abe, Ikuo Shoji

  Lysosome incorporate and degrade proteins in a process known as autophagy. There are three types of autophagy; macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). Although autophagy is considered a nonselective degradation process, CMA is known as a selective degradation pathway. All proteins internalized in the lysosome via CMA contain a pentapeptide KFERQ-motif, also known as a CMA-targeting motif, which is necessary for selectivity. CMA directly delivers a substrate protein into the lysosome lumen using the cytosolic chaperone HSC70 and the lysosomal receptor LAMP-2A for degradation. Hepatitis C virus (HCV) NS5A protein interacts with hepatocyte-nuclear factor 1α (HNF-1α) together with HSC70 and promotes the lysosomal degradation of HNF-1α via CMA, resulting in HCV-induced pathogenesis. HCV NS5A promotes recruitment of HSC70 to the substrate protein HNF-1α. HCV NS5A plays a crucial role in HCV-induced CMA. Further investigations of HCV NS5A-interacting proteins containing CMA-targeting motifs may help to elucidate HCV-induced pathogenesis.

  2021年, Frontiers in cellular and infection microbiology, 11, 796664 - 796664, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• ISGylation of hepatitis C virus NS5A protein promotes viral RNA replication via the recruitment of cyclophilin A.

  Takayuki Abe, Nanae Minami, Rheza Gandi Bawono, Chieko Matsui, Lin Deng, Takasuke Fukuhara, Yoshiharu Matsuura, Ikuo Shoji

  Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like protein that is covalently conjugated to many substrate proteins in order to modulate their functions; this conjugation is called 'ISGylation'. Several groups reported that the ISGylation of hepatitis C virus (HCV) NS5A protein affects HCV replication. However, ISG15 conjugation sites on NS5A are not well determined, and it is unclear whether the role of NS5A-ISGylation in HCV replication is pro-viral or anti-viral. Here we investigated the role of NS5A-ISGylation in HCV replication by using HCV RNA replicons that have a mutation at each lysine (Lys) residue of NS5A protein. Immunoblot analyses revealed that five Lys residues (K44, K68, K166, K215, and K308) of 14 Lys residues within NS5A (1b, Con1) have the potential to accept ISGylation. We tested the NS5A-ISGylation among different HCV genotypes and observed that the NS5A of all of the HCV genotypes accept ISGylation at the multiple Lys residues. Using an HCV luciferase reporter replicon assay revealed that the residue K308 of NS5A is important for HCV (1b, Con1) RNA replication. We observed that K308, one of the Lys residues for NS5A-ISGylation, is located within the binding region of cyclophilin A (CypA), which is the critical host factor for HCV replication. We obtained evidence suggesting that NS5A-ISGylation derived from all of HCV genotypes enhances the interaction between NS5A and CypA. Taken together, these results suggest that NS5A-ISGylation functions as a pro-viral factor and promotes HCV replication via the recruitment of CypA.IMPORTANCEHost cells have evolved host defense machinery (such as innate immunity) to eliminate viral infections. Viruses have evolved several counteracting strategies for achieving an immune escape from host defense machinery, including type-I interferons (IFNs) and inflammatory cytokines. ISG15 is an IFN-inducible, ubiquitin-like protein that is covalently conjugated to the viral protein via specific Lys residues and suppresses viral functions and viral propagation. Here we demonstrate that HCV NS5A protein accepts ISG15-conjugation at specific Lys residues and that the HERC5 E3 ligase specifically promotes NS5A-ISGylation. We obtained evidence suggesting that NS5A-ISGylation facilitates the recruitment of CypA, which is the critical host factor for HCV replication, thereby promoting HCV replication. These findings indicate that E3 ligase HERC5 is a potential therapeutic target for HCV infection. We propose that HCV hijacks an intracellular ISG15 function to escape the host defense machinery in order to establish a persistent infection.

  2020年07月, Journal of virology, 94(20) (20), 英語, 国際誌, 国際共著している

  [査読有り]

  研究論文（学術雑誌）


• G2P[4] rotavirus outbreak in Belu, East Nusa Tenggara Province, Indonesia, 2018.

  Takako Utsumi, Rury M Wahyuni, Zayyin Dinana, Emily Gunawan, Arga S D Putra, Teguh Mubawadi, Soetjipto, Maria I Lusida, Ikuo Shoji

  Rotavirus is a major cause of acute gastroenteritis (AGE) in children worldwide. However, rotavirus outbreak has rarely been reported in Indonesia. This study aims to identify the causative agent for AGE outbreak among children in Belu, East Nusa Tenggara, Indonesia in 2018. All the samples were negative for bacteria (Salmonella, V. cholera) and Norovirus. Ten out of 11 stool samples were rotavirus-positive by immunochromatography testing. Reverse-transcription polymerase chain reaction (RT-PCR) and phylogenetic analyses revealed that rotavirus G2P[4] was the possible causative agent for the AGE outbreak, although sample size was limited. These findings suggest that the AGE outbreak was caused by rotavirus G2P[4], highlighting the importance of rotavirus surveillance.

  2020年05月, Journal of infection and public health, 英語, 国際誌, 国際共著している

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Predominance of norovirus GI.4 from children with acute gastroenteritis in Jambi, Indonesia, 2019.

  Putri Sari Wulandari, Juniastuti, Rury Mega Wahyuni, Mochamad Amin, Laura Navika Yamani, Muhammad Qushai Yunifiar Matondang, Zayyin Dinana, Soetjipto, Takako Utsumi, Ikuo Shoji, Maria Inge Lusida

  Norovirus (NoV) is one of the most important viral causes of acute gastroenteritis (AGE) in children worldwide. Only a few studies have reported AGE with NoV-positive in some cities in Indonesia. This study aimed to investigate the incidence and clinical characteristic of NoV infection, and also genotype distribution of NoV in children with AGE in Jambi, as the capital and the largest city of Jambi province, Indonesia. Stool samples were collected from children (≤15 years of age) with AGE at three participating hospitals in Jambi from February to April 2019. The detection of NoV and its genotyping were carried out by reverse-transcriptase polymerase chain reaction and direct sequencing. Of the 91 stool samples collected, 14 (15.4%) were positive for NoV. Fever, vomiting, and severe diarrhea were commonly observed in AGE with NoV, while level of dehydration was statistically significant difference between children with NoV-positive and those with NoV-negative. The most prevalent genotype was GI.4 (42.9%), followed by GII.6 (28.6%) and some other genotypes. Interestingly, this study found the predominance of GI.4, differed from previous reports in Indonesia. Continuously investigation of the circulating genotype is needed to control the NoV-infected AGE.

  2020年05月, Journal of medical virology, 英語, 国際誌, 国際共著している

  [査読有り]

  研究論文（学術雑誌）


• Peroxiredoxin 1, a Novel HBx-Interacting Protein, Interacts with Exosome Component 5 and Negatively Regulates Hepatitis B Virus (HBV) Propagation through Degradation of HBV RNA.

  Deng L, Gan X, Ito M, Chen M, Aly HH, Matsui C, Abe T, Watashi K, Wakita T, Suzuki T, Okamoto T, Matsuura Y, Mizokami M, Shoji I, Hotta H

  2019年03月, Journal of virology, 93(6) (6), 国際誌, 国際共著している

  [査読有り]

  研究論文（学術雑誌）


• Post-vaccinated asymptomatic rotavirus infections: A community profile study of children in Surabaya, Indonesia.

  Gunawan E, Utsumi T, Wahyuni RM, Dinana Z, Sudarmo SM, Shoji I, Soetjipto, Lusida MI

  2019年03月, Journal of infection and public health, 国際誌, 国際共著している

  [査読有り]

  神戸大学リポジトリ（Kernel）へのリンク


• Cytosolic DNA-sensing immune response and viral infection.

  Takayuki Abe, Yuki Marutani, Ikuo Shoji

  How host cells recognize many kinds of RNA and DNA viruses and initiate innate antiviral responses against them has not yet been fully elucidated. Over the past decade, investigations into the mechanisms underlying these antiviral responses have focused extensively on immune surveillance sensors that recognize virus-derived components (such as lipids, sugars and nucleic acids). The findings of these studies have suggested that antiviral responses are mediated by cytosolic or intracellular compartment sensors and their adaptor molecules (e.g., TLR, myeloid differentiation primary response 88, retinoic acid inducible gene-I, IFN-β promoter stimulator-1, cyclic GMP-AMP synthase and stimulator of IFN genes axis) for the primary sensing of virus-derived nucleic acids, leading to production of type I IFNs, pro-inflammatory cytokines and chemokines by the host cells. Thus, host cells have evolved an elaborate host defense machinery to recognize and eliminate virus infections. In turn, to achieve sustained viral infection and induce pathogenesis, viruses have also evolved several counteracting strategies for achieving immune escape by targeting immune sensors, adaptor molecules, intracellular kinases and transcription factors. In this review, we discuss recent discoveries concerning the role of the cytosolic nucleic acid-sensing immune response in viral recognition and control of viral infection. In addition, we consider the regulatory machinery of the cytosolic nucleic acid-sensing immune response because these immune surveillance systems must be tightly regulated to prevent aberrant immune responses to self and non-self-nucleic acids.

  2019年02月, Microbiology and immunology, 63(2) (2), 51 - 64, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Molecular Epidemiology and Clinical Features of Rotavirus Infection Among Pediatric Patients in East Java, Indonesia During 2015-2018: Dynamic Changes in Rotavirus Genotypes From Equine-Like G3 to Typical Human G1/G3.

  Alpha Fardah Athiyyah, Takako Utsumi, Rury Mega Wahyuni, Zayyin Dinana, Laura Navika Yamani, Soetjipto, Subijanto Marto Sudarmo, Reza Gunadi Ranuh, Andy Darma, Juniastuti, Dadik Raharjo, Chieko Matsui, Lin Deng, Takayuki Abe, Yen Hai Doan, Yoshiki Fujii, Hiroyuki Shimizu, Kazuhiko Katayama, Maria Inge Lusida, Ikuo Shoji

  2019年, Frontiers in microbiology, 10, 940 - 940, 英語, 国際誌, 国際共著している

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Improvement of Rotavirus Genotyping Method by Using the Semi-Nested Multiplex-PCR With New Primer Set.

  Yoshiki Fujii, Yen Hai Doan, Rury Mega Wahyuni, Maria Inge Lusida, Takako Utsumi, Ikuo Shoji, Kazuhiko Katayama

  Rotavirus A (RVA) is a major cause of gastroenteritis in infants and young children. After vaccine introduction, RVA surveillance has become more important for monitoring changes in genotype distribution, and the semi-nested multiplex-PCR is a popular method for RVA genotyping. In particular, the VP7 primer set reported by Gouvea and colleagues in 1990 is still widely used worldwide as the recommended WHO primer set in regional and national reference RVA surveillance laboratories. However, this primer set yielded some mistakes with recent epidemic strains. The newly emerged equine-like G3 strains were mistyped as G1, G8 strains were mistyped as G3, the G9 lineage 3 strains showed very weak band, and the G9 lineage 6 strains showed a G9-specific band and a non-specific band. Gouvea's standard protocol has become relatively unreliable for identifying genotypes correctly. To overcome this limitation, we redesigned the primer set to include recent epidemic strains. Our new primer set enabled us to correctly identify the VP7 genotypes of representative epidemic strains by agarose gel electrophoresis (G1, G2, human typical G3, equine-like G3, G4, G8, G9, and G12). We believe that the multiplex-PCR method with our new primer set is a useful and valuable tool for surveillance of RVA epidemics.

  2019年, Frontiers in microbiology, 10, 647 - 647, 英語, 国際誌, 国際共著している

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Hepatitis C virus NS5A protein promotes the lysosomal degradation of hepatocyte nuclear factor 1α via chaperone-mediated autophagy.

  Matsui C, Deng L, Minami N, Abe T, Koike K, Shoji I

  American Society for Microbiology, 2018年07月, Journal of virology, 92(13) (13), 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Equine-like G3 rotavirus strains as predominant strains among children in Indonesia in 2015-2016.

  Takako Utsumi, Rury Mega Wahyuni, Yen Hai Doan, Zayyin Dinana, Soegeng Soegijanto, Yoshiki Fujii, Juniastuti, Laura Navika Yamani, Chieko Matsui, Lin Deng, Takayuki Abe, Soetjipto, Maria Inge Lusida, Koji Ishii, Hiroyuki Shimizu, Kazuhiko Katayama, Ikuo Shoji

  Rotavirus A (RVA) is a major cause of acute gastroenteritis in humans and animals worldwide. As a result of the segmented nature of the rotavirus genome, genetic reassortment commonly occurs. This study aims to clarify the genetic characteristics of RVAs circulating in Indonesia. From June 2015 through August 2016, stool samples were collected from 134 children aged <5 years (71 male and 63 female) with acute gastroenteritis who were inpatients at a private hospital in Surabaya, Indonesia. All stool samples were screened for RVA antigen using immunochromatography. Forty-two samples (31.3%, 42/134) were RVA antigen-positive. All RVA positive samples tested showed the unusual combinations of G3P[8] (n = 36) and G3P[6] (n = 3) with a short RNA pattern by G/P typing and polyacrylamide gel electrophoresis (PAGE). Whole genome analysis by next-generation sequencing (NGS) was performed for 11 strains to determine the RVA genotypes. Eleven rotavirus strains were found to carry a DS-like genetic backbone; nine strains showed a G3-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2 genome constellation, which was recently reported in Australia, Hungary, Spain and Brazil; as well, two strains showed a G3-P[6]-I2-R2-C2-M2-A2-N2-T2-E2-H2 genome constellation. The phylogenetic tree based on the VP7 gene showed that all 11 strains were classified as equine-like G3, which is genetically distinct and different in origin from typical human G3 strains. The phylogenetic tree based on the NSP4 gene showed that six strains were classified as bovine-like strain and the remaining five were classified as human strain. In conclusion, we identified the strains which are intergenogroup reassortants containing an equine-like G3 VP7, a P[8])/P[6] VP4, with a DS-1-like genetic backbone. These findings suggest that equine-like G3P[8] and P[6] RVA strains have been circulating in the Indonesian population for at least 1 year and probably longer, indicating a diversity of RVAs in this area.

  2018年07月, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 61, 224 - 228, 英語, 国際誌, 国際共著している

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• 脱ユビキチン化酵素USP15阻害剤候補分子の機能解析

  勝二 郁夫, 松井 千絵子, Deng Lin, 阿部 隆之

  生命科学系学会合同年次大会運営事務局, 2017年12月, 生命科学系学会合同年次大会, 2017年度, [3LBA - 019], 日本語


• Occurrence of norovirus infection in an asymptomatic population in Indonesia

  Takako Utsumi, Maria Inge Lusida, Zayyin Dinana, Rury Mega Wahyuni, Laura Navika Yamani, Juniastuti, Soetjipto, Chieko Matsui, Lin Deng, Takayuki Abe, Yen Hai Doan, Yoshiki Fujii, Hirokazu Kimura, Kazuhiko Katayama, Ikuo Shoji

  2017年11月, INFECTION GENETICS AND EVOLUTION, 55, 1 - 7, 英語, 国際誌, 国際共著している

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Unconjugated interferon-stimulated gene 15 specifically interacts with the hepatitis C virus NS5A protein via domain I

  Nanae Minami, Takayuki Abe, Lin Deng, Chieko Matsui, Takasuke Fukuhara, Yoshiharu Matsuura, Ikuo Shoji

  2017年07月, MICROBIOLOGY AND IMMUNOLOGY, 61(7) (7), 287 - 292, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• TRIM32-Cytoplasmic-Body Formation Is an ATP-Consuming Process Stimulated by HSP70 in Cells

  Yuki Kawaguchi, Masato Taoka, Takahiro Takekiyo, Takamasa Uekita, Ikuo Shoji, Naomi Hachiya, Tohru Ichimura

  2017年01月, PLOS ONE, 12(1) (1), e0169436, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Hepatitis C virus NS5A protein interacts with lysine methyltransferase SET and MYND domain-containing 3 and induces activator protein 1 activation

  Ming Chen, Xiang Gan, Ken-ichi Yoshino, Madoka Kitakawa, Ikuo Shoji, Lin Deng, Hak Hotta

  2016年06月, MICROBIOLOGY AND IMMUNOLOGY, 60(6) (6), 407 - 417, 英語, 国際誌, 国際共著している

  [査読有り]

  研究論文（学術雑誌）


• TRC8-dependent degradation of hepatitis C virus immature core protein regulates viral propagation and pathogenesis

  Sayaka Aizawa, Toru Okamoto, Yukari Sugiyama, Takahisa Kouwaki, Ayano Ito, Tatsuya Suzuki, Chikako Ono, Takasuke Fukuhara, Masahiro Yamamoto, Masayasu Okochi, Nobuhiko Hiraga, Michio Imamura, Kazuaki Chayama, Ryosuke Suzuki, Ikuo Shoji, Kohji Moriishi, Kyoji Moriya, Kazuhiko Koike, Yoshiharu Matsuura

  2016年05月, NATURE COMMUNICATIONS, 7, 11379, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Interaction of the hepatitis B virus X protein with the lysine methyltransferase SET and MYND domain-containing 3 induces activator protein 1 activation

  Miwako Hayashi, Lin Deng, Ming Chen, Xiang Gan, Kenta Shinozaki, Ikuo Shoji, Hak Hotta

  2016年01月, MICROBIOLOGY AND IMMUNOLOGY, 60(1) (1), 17 - 25, 英語, 国際誌, 国際共著している

  [査読有り]

  研究論文（学術雑誌）


• 脱ユビキチン化酵素USP15阻害剤の探索

  勝二 郁夫, Sianipar Imelda Rosalyn, 南 奈苗, 陳 明, 松井 千絵子, Lin Deng

  (公社)日本生化学会, 2015年12月, 日本生化学会大会・日本分子生物学会年会合同大会講演要旨集, 88回・38回, [1P0487] - [1P0487], 日本語


• HCV upregulates Bim through the ROS/JNK signalling pathway, leading to Bax-mediated apoptosis

  Lin Deng, Ming Chen, Motofumi Tanaka, Yonson Ku, Tomoo Itoh, Ikuo Shoji, Hak Hotta

  2015年09月, JOURNAL OF GENERAL VIROLOGY, 96(9) (9), 2670 - 2683, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• A single-amino-acid mutation in hepatitis C virus NS5A disrupts physical and functional interaction with the transcription factor HNF-1α.

  Matsui C, Rosalyn Sianipar I, Minami N, Deng L, Hotta H, Shoji I

  2015年08月, The Journal of general virology, 96(8) (8), 2200 - 2205, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Physical and functional interaction between hepatitis C virus NS5A protein and ovarian tumor protein deubiquitinase 7B

  Imelda Rosalyn Sianipar, Chieko Matsui, Nanae Minami, Xiang Gan, Lin Deng, Hak Hotta, Ikuo Shoji

  2015年08月, MICROBIOLOGY AND IMMUNOLOGY, 59(8) (8), 466 - 476, 英語, 国際誌, 国際共著している

  [査読有り]

  研究論文（学術雑誌）


• [Hepatitis C virus-induced glucose metabolic disorder].

  Ikuo Shoji, Lin Deng, Chieko Matsui, Hak Hotta

  Hepatitis C virus (HCV) infection often causes intrahepatic diseases, such as chronic hepatitis, liver chirrohsis, and hepatocellular carcinoma (HCC). Moreover, HCV infection exhibits various extrahepatic manifestations, such as thyroiditis, glucose and lipid metabolic disorder, and iron metabolic disorder. HCV infection is often associated with type 2 diabetes, involving hepatic fibrosis and poor prognosis. Type 2 diabetes increases the risk of HCC. We have been investigating molecular mechanisms of HCV-induced glucose metabolic disorder and we reported that HCV infection promotes hepatic gluconeogenesis through forkhead box O1 (FoxO1)-dependent pathway and that HCV infection suppresses the cell surface expression of glucose transporter 2 (GLUT2), resulting in suppression of glucose uptake. We have found that HCV NS5A protein plays important roles in these two independent pathways. Here we discuss the roles of HCV NS5A in HCV-induced glucose metabolic disorder.

  2015年, Uirusu, 65(2) (2), 263 - 268, 日本語, 国内誌

  研究論文（学術雑誌）


• Nitrosative Stress Induces Peroxiredoxin 1 Ubiquitination During Ischemic Insult via E6AP Activation in Endothelial Cells Both In Vitro and In Vivo

  Rong-Rong Tao, Huan Wang, Ling-Juan Hong, Ji-Yun Huang, Ying-Mei Lu, Mei-Hua Liao, Wei-Feng Ye, Nan-Nan Lu, Dan-Yan Zhu, Qian Huang, Kohji Fukunaga, Yi-Jia Lou, Ikuo Shoji, Christopher Stuart Wilcox, En-Yin Lai, Feng Han

  2014年07月, ANTIOXIDANTS & REDOX SIGNALING, 21(1) (1), 1 - 16, 英語, 国際誌, 国際共著している

  [査読有り]

  研究論文（学術雑誌）


• Induction of Cell-Mediated Immune Responses in Mice by DNA Vaccines That Express Hepatitis C Virus NS3 Mutants Lacking Serine Protease and NTPase/RNA Helicase Activities

  Suratno Lulut Ratnoglik, Da-Peng Jiang, Chie Aoki, Pratiwi Sudarmono, Ikuo Shoji, Lin Deng, Hak Hotta

  2014年06月, PLOS ONE, 9(6) (6), e98877, 英語, 国際誌, 国際共著している

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Anti-hepatitis C virus compounds obtained from Glycyrrhiza uralensis and other Glycyrrhiza species

  Myrna Adianti, Chie Aoki, Mari Komoto, Lin Deng, Ikuo Shoji, Tutik Sri Wahyuni, Maria Inge Lusida, Soetjipto, Hiroyuki Fuchino, Nobuo Kawahara, Hak Hotta

  2014年03月, MICROBIOLOGY AND IMMUNOLOGY, 58(3) (3), 180 - 187, 英語, 国際誌, 国際共著している

  [査読有り]

  研究論文（学術雑誌）


• Antiviral activity of extracts from Morinda citrifolia leaves and chlorophyll catabolites, pheophorbide a and pyropheophorbide a, against hepatitis C virus

  Suratno Lulut Ratnoglik, Chie Aoki, Pratiwi Sudarmono, Mari Komoto, Lin Deng, Ikuo Shoji, Hiroyuki Fuchino, Nobuo Kawahara, Hak Hotta

  2014年03月, MICROBIOLOGY AND IMMUNOLOGY, 58(3) (3), 188 - 194, 英語, 国際誌, 国際共著している

  [査読有り]

  研究論文（学術雑誌）


• Hepatitis C Virus NS3/4A Protease Inhibits Complement Activation by Cleaving Complement Component 4

  Seiichi Mawatari, Hirofumi Uto, Akio Ido, Kenji Nakashima, Tetsuro Suzuki, Shuji Kanmura, Kotaro Kumagai, Kohei Oda, Kazuaki Tabu, Tsutomu Tamai, Akihiro Moriuchi, Makoto Oketani, Yuko Shimada, Masayuki Sudoh, Ikuo Shoji, Hirohito Tsubouchi

  2013年12月, PLOS ONE, 8(12) (12), e82094, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Antiviral activities of Indonesian medicinal plants in the East Java region against hepatitis C virus

  Tutik Sri Wahyuni, Lydia Tumewu, Adita Ayu Permanasari, Evhy Apriani, Myrna Adianti, Abdul Rahman, Aty Widyawaruyanti, Maria Inge Lusida, Achmad Fuad, Soetjipto, Nasronudin, Hiroyuki Fuchino, Nobuo Kawahara, Ikuo Shoji, Lin Deng, Chie Aoki, Hak Hotta

  2013年08月, VIROLOGY JOURNAL, 10, 259, 英語, 国際誌, 国際共著している

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Polymorphisms of the core, NS3, and NS5A proteins of hepatitis C virus genotype 1b associate With development of hepatocellular carcinoma

  Ahmed El-Shamy, Michiko Shindo, Ikuo Shoji, Lin Deng, Tadao Okuno, Hak Hotta

  2013年08月, HEPATOLOGY, 58(2) (2), 555 - 563, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• 14-3-3 proteins sequester a pool of soluble TRIM32 ubiquitin ligase to repress autoubiquitylation and cytoplasmic body formation

  Tohru Ichimura, Masato Taoka, Ikuo Shoji, Hiroki Kato, Tomonobu Sato, Shigetsugu Hatakeyama, Toshiaki Isobe, Naomi Hachiya

  2013年05月, JOURNAL OF CELL SCIENCE, 126(9) (9), 2014 - 2026, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Hepatitis C virus infection suppresses GLUT2 gene expression via downregulation of hepatocyte nuclear factor 1α.

  Matsui C, Shoji I, Kaneda S, Sianipar IR, Deng L, Hotta H

  2012年12月, Journal of virology, 86(23) (23), 12903 - 12911, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• NS5A Sequence Heterogeneity of Hepatitis C Virus Genotype 4a Predicts Clinical Outcome of Pegylated-Interferon-Ribavirin Therapy in Egyptian Patients

  Ahmed El-Shamy, Ikuo Shoji, Wafaa El-Akel, Shymaa E. Bilasy, Lin Deng, Maissa El-Raziky, Da-peng Jiang, Gamal Esmat, Hak Hotta

  2012年12月, JOURNAL OF CLINICAL MICROBIOLOGY, 50(12) (12), 3886 - 3892, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Prediction of response to pegylated interferon/ribavirin combination therapy for chronic hepatitis C genotype 1b and high viral load

  Soo Ryang Kim, Ahmed El-Shamy, Susumu Imoto, Ke Ih Kim, Yoshi-hiro Ide, Lin Deng, Ikuo Shoji, Yasuhito Tanaka, Yutaka Hasegawa, Mitsuhiro Ota, Hak Hotta

  2012年10月, JOURNAL OF GASTROENTEROLOGY, 47(10) (10), 1143 - 1151, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• HCV NS5A Protein Containing Potential Ligands for Both Src Homology 2 and 3 Domains Enhances Autophosphorylation of Src Family Kinase Fyn in B Cells

  Kenji Nakashima, Kenji Takeuchi, Kazuyasu Chihara, Tomoko Horiguchi, Xuedong Sun, Lin Deng, Ikuo Shoji, Hak Hotta, Kiyonao Sada

  2012年10月, PLOS ONE, 7(10) (10), 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• HCV NS5A protein containing potential ligands for both Src homology 2 and 3 domains enhances autophosphorylation of Src family kinase Fyn in B cells

  K. Sada, K. Nakashima, K. Takeuchi, K. Chihara, T. Horiguchi, L. Deng, I. Shoji, H. Hotta

  2012年09月, FEBS JOURNAL, 279, 161 - 162, 英語, 国際誌

  [査読有り]


• Roles of the two distinct proteasome pathways in hepatitis C virus infection.

  Shoji I

  2, 2012年04月, World journal of virology, 1, 44 - 50, 国際誌

  [査読有り]


• PEG-IFN/RBV(2者併用療法)の治療効果に関係するウイルス因子とウイルス排除機序の検討

  堀田博, 井出良浩, 勝二郁夫

  (一社)日本肝臓学会, 2012年04月, 肝臓, 53(Suppl.1) (Suppl.1), A530 - A527, 日本語, 国内誌

  [査読有り]

  研究論文（その他学術会議資料等）


• PEG-IFN/RBV(2者併用療法)のSVR予測におけるIRRDR変異数の検討

  井出良浩, 勝二郁夫, 堀田博

  (一社)日本肝臓学会, 2012年04月, 肝臓, 53(Suppl.1) (Suppl.1), A529 - A527, 日本語, 国内誌

  [査読有り]

  研究論文（その他学術会議資料等）


• C型肝炎臨床 2者併用療法におけるrelapse例とNVR例の3者併用療法時SVR予測の試み

  堀田博, 井出良浩, 勝二郁夫

  2012年04月, 肝臓, 53(Suppl.1) (Suppl.1), A355, 日本語, 国内誌

  [査読有り]

  研究論文（その他学術会議資料等）


• A point mutation at Asn-534 that disrupts a conserved N-glycosylation motif of the E2 glycoprotein of hepatitis C virus markedly enhances the sensitivity to antibody neutralization

  Mikiko Sasayama, Ikuo Shoji, Myrna Adianti, Da-Peng Jiang, Lin Deng, Takafumi Saito, Hisayoshi Watanabe, Sumio Kawata, Chie Aoki, Hak Hotta

  2012年02月, JOURNAL OF MEDICAL VIROLOGY, 84(2) (2), 229 - 234, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Sequence Heterogeneity in NS5A of Hepatitis C Virus Genotypes 2a and 2b and Clinical Outcome of Pegylated-Interferon/Ribavirin Therapy

  Ahmed El-Shamy, Ikuo Shoji, Soo-Ryang Kim, Yoshihiro Ide, Susumu Imoto, Lin Deng, Seitetsu Yoon, Takashi Fujisawa, Satoshi Tani, Yoshihiko Yano, Yasushi Seo, Takeshi Azuma, Hak Hotta

  2012年02月, PLOS ONE, 7(2) (2), e30513, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Polymorphisms of Hepatitis C Virus Non-Structural Protein 5A and Core Protein and Clinical Outcome of Pegylated-Interferon/Ribavirin Combination Therapy

  Ahmed El-Shamy, Soo-Ryang Kim, Yoshi-Hiro Ide, Noriko Sasase, Susumu Imoto, Lin Deng, Ikuo Shoji, Hak Hotta

  2012年, INTERVIROLOGY, 55(1) (1), 1 - 11, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Generation of a recombinant reporter hepatitis C virus useful for the analyses of virus entry, intra-cellular replication and virion production

  Kazuya Kamada, Ikuo Shoji, Lin Deng, Chie Aoki, Suratno Lulut Ratnoglik, Takaji Wakita, Hak Hotta

  2012年01月, MICROBES AND INFECTION, 14(1) (1), 69 - 78, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Molecular mechanism of hepatitis C virus-induced glucose metabolic disorders

  Ikuo Shoji, Lin Deng, Hak Hotta

  2012年, FRONTIERS IN MICROBIOLOGY, 3, 278, 英語, 国際誌

  [査読有り]


• Natural Product-Like Macrocyclic N-Methyl-Peptide Inhibitors against a Ubiquitin Ligase Uncovered from a Ribosome-Expressed De Novo Library

  Yusuke Yamagishi, Ikuo Shoji, Shoji Miyagawa, Takashi Kawakami, Takayuki Katoh, Yuki Goto, Hiroaki Suga

  2011年12月, CHEMISTRY & BIOLOGY, 18(12) (12), 1562 - 1570, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Hepatitis C Virus Infection Promotes Hepatic Gluconeogenesis through an NS5A-Mediated, FoxO1-Dependent Pathway

  Lin Deng, Ikuo Shoji, Wataru Ogawa, Shusaku Kaneda, Tomoyoshi Soga, Da-peng Jiang, Yoshi-Hiro Ide, Hak Hotta

  2011年09月, JOURNAL OF VIROLOGY, 85(17) (17), 8556 - 8568, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• C型慢性肝炎に対するPEG-IFNα-2b+Ribavirin(併用療法)におけるインスリン抵抗性と治療効果、肝組織所見、BMIとの関連

  金 守良, 井本 勉, 堀田 博, 谷口 美幸, 金 啓二, El Shamy A., 勝二 郁夫, 林 祥剛, 土田 忍, 外山 博近, 田中 基文, 前川 陽子

  (一社)日本肝臓学会, 2011年09月, 肝臓, 52(Suppl.2) (Suppl.2), A663 - A663, 日本語, 国内誌

  [査読有り]


• C型肝炎ウイルスのNS3変異Y56/Q86及びコア蛋白変異Q70は高発癌性ウイルス株の指標となる

  勝二郁夫, 堀田博

  2011年09月, 肝臓, 52巻, Suppl.2, pp. A652-A652, 日本語, 国内誌

  研究論文（国際会議プロシーディングス）


• C型慢性肝炎に対するPEG-IFNα-2a/RBV併用療法のEVR・SVRに関与する因子の検討(神戸肝炎治療研究会)

  瀬尾靖, 勝二郁夫, 堀田博, 東健

  2011年09月, 肝臓, 52巻, Suppl.2, pp. A597-A597, 日本語, 国際誌

  [査読有り]

  研究論文（国際会議プロシーディングス）


• Sequence heterogeneity of NS5A and core proteins of hepatitis C virus and virological responses to pegylated-interferon/ribavirin combination therapy

  Ahmed El-Shamy, Ikuo Shoji, Takafumi Saito, Hisayoshi Watanabe, Yoshi-Hiro Ide, Lin Deng, Sumio Kawata, Hak Hotta

  2011年06月, MICROBIOLOGY AND IMMUNOLOGY, 55(6) (6), 418 - 426, 英語

  [査読有り]

  研究論文（学術雑誌）


• 併用療法無効患者に対する二重濾過血漿交換療法(DFPP)のEVRに関係するウイルスダイナミックス、宿主因子(IL28B)とウイルス因子の検討

  金 守良, 井本 勉, 堀田 博, 土田 忍, 外山 博近, 田中 基文, 前川 陽子, 谷口 美幸, 金 啓二, 勝二 郁夫, 長野 基子, 井出 良浩

  (一社)日本肝臓学会, 2011年04月, 肝臓, 52(Suppl.1) (Suppl.1), A303 - A303, 日本語

  [査読有り]


• ウイルス肝炎・肝癌制圧の分子基盤 HCV NS3トランスジェニックマウスを用いた肝発癌機構の研究

  勝二郁夫, 堀田博

  2011年04月, 肝臓, 52巻, Suppl.1, pp. A24-A24, 日本語

  研究論文（国際会議プロシーディングス）


• C型肝炎ウイルスは酸化ストレスを介して糖新生を亢進し糖尿病発症に関与する

  勝二郁夫, 堀田博

  2011年04月, 肝臓, 52巻, Suppl.1, pp. A144-A144, 日本語

  研究論文（国際会議プロシーディングス）


• 亜急性硬化性全脳炎(SSPE)マウスモデルの作製と神経病変の解析

  勝二郁夫, 堀田博

  2011年03月, 日本病理学会会誌, 100巻, 1号, pp. 421-421, 日本語

  研究論文（国際会議プロシーディングス）


• Chaperonin TRiC/CCT participates in replication of hepatitis C virus genome via interaction with the viral NS5B protein

  Yasushi Inoue, Hideki Aizaki, Hiromichi Hara, Mami Matsuda, Tomomi Ando, Tetsu Shimoji, Kyoko Murakami, Takahiro Masaki, Ikuo Shoji, Sakae Homma, Yoshiharu Matsuura, Tatsuo Miyamura, Takaji Wakita, Tetsuro Suzuki

  2011年02月, VIROLOGY, 410(1) (1), 38 - 47, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• 17β-estradiol inhibits the production of infectious particles of hepatitis C virus.

  Hayashida K, Shoji I, Deng L, Jiang DP, Ide YH, Hotta H

  2010年11月, Microbiology and immunology, 54(11) (11), 684 - 690, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• E6AP Ubiquitin Ligase Mediates Ubiquitin-Dependent Degradation of Peroxiredoxin 1

  Junichi Nasu, Kyoko Murakami, Shoji Miyagawa, Ryosuke Yamashita, Tohru Ichimura, Takaji Wakita, Hak Hotta, Tatsuo Miyamura, Tetsuro Suzuki, Tazuko Satoh, Ikuo Shoji

  2010年10月, JOURNAL OF CELLULAR BIOCHEMISTRY, 111(3) (3), 676 - 685, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• C型慢性肝炎1b型高ウイルス量併用療法無効患者に対する二重濾過血漿交換療法(DFPP) IFNβ2〜4週連続投与後PEG-IFNα-2a RBV併用療法の早期ウイルスダイナミックスによるEVR予測

  堀田博, 勝二郁夫, 井出良浩

  2010年09月, 肝臓, 51巻, Suppl.2, pp. A591-A591, 日本語

  研究論文（国際会議プロシーディングス）


• Secondary Structure of the Amino-Terminal Region of HCV NS3 and Virological Response to Pegylated Interferon Plus Ribavirin Therapy for Chronic Hepatitis C

  Mai Sanjo, Takafumi Saito, Rika Ishii, Yuko Nishise, Hiroaki Haga, Kazuo Okumoto, Junitsu Ito, Hisayoshi Watanabe, Koji Saito, Hitoshi Togashi, Kazuto Fukuda, Yasuharu Imai, Ahmed El-Shamy, Lin Deng, Ikuo Shoji, Hak Hotta, Sumio Kawata

  2010年08月, JOURNAL OF MEDICAL VIROLOGY, 82(8) (8), 1364 - 1370, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Involvement of PA28 gamma in the Propagation of Hepatitis C Virus

  Kohji Moriishi, Ikuo Shoji, Yoshio Mori, Ryosuke Suzuki, Tetsuro Suzuki, Chikako Kataoka, Yoshiharu Matsuura

  2010年08月, HEPATOLOGY, 52(2) (2), 411 - 420, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• 慢性C型肝炎に対するPEG-IFN/RBV治療効果に及ぼすウイルス側因子のさらなる検討 HCV-2a及びHCV-2bのNS5A多様性は治療効果と相関する

  堀田博, 井出良浩, 勝二郁夫

  2010年04月, 肝臓, 51巻, Suppl.1, pp. A231-A231, 日本語

  研究論文（国際会議プロシーディングス）


• 1b型高ウイルスC型慢性肝炎のPEG-IFN リバビリン併用療法(併用療法)無効例に対する二重濾過血漿交換療法(DFPP) IFN-β4週間連続投与の試み

  堀田博, 勝二郁夫

  2010年04月, 肝臓, 51巻, Suppl.1, pp. A287-A287, 日本語

  研究論文（国際会議プロシーディングス）


• FAM20A exon1欠損が成長発育に及ぼす影響

  井出良浩, 勝二郁夫, 堀田博

  (一社)日本解剖学会, 2010年03月, 解剖学雑誌, 85巻, Suppl., pp. 186-186(Suppl.) (Suppl.), 186 - 186, 日本語

  研究論文（国際会議プロシーディングス）


• Double-Filtration Plasmapheresis plus IFN for HCV-1b Patients with Non-Sustained Virological Response to Previous Combination Therapy: Early Viral Dynamics

  Soo Ryang Kim, Susumu Imoto, Masatoshi Kudo, Keiji Mita, Miyuki Taniguchi, Ke Ih Kim, Noriko Sasase, Ikuo Shoji, Motoko Nagano-Fujii, Ahmed El-Shamy, Hak Hotta, Tomoyuki Nagai, Yoshiaki Nagata, Yoshitake Hayashi

  2010年, INTERVIROLOGY, 53(1) (1), 44 - 48, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Outcome and Early Viral Dynamics with Viral Mutation in PEG-IFN/RBV Therapy for Chronic Hepatitis in Patients with High Viral Loads of Serum HCV RNA Genotype 1b

  Noriko Sasase, Soo Ryang Kim, Masatoshi Kudo, Ke Ih Kim, Miyuki Taniguchi, Susumu Imoto, Keiji Mita, Yoshitake Hayashi, Ikuo Shoji, Ahmed El-Shamy, Hak Hotta

  2010年, INTERVIROLOGY, 53(1) (1), 49 - 54, 英語

  [査読有り]

  研究論文（学術雑誌）


• Autoimmune thrombocytopenic purpura during pegylated interferon α treatment for chronic hepatitis C.

  Kim SR, Imoto S, Kudo M, Nakajima T, Ando K, Mita K, Fukuda K, Hong HS, Lee YH, Nakashima K, Shoji I, Nagano-Fujii M, Hotta H, Hayashi Y

  2010年, Internal medicine (Tokyo, Japan), 49(12) (12), 1119 - 1122, 英語

  [査読有り]

  研究論文（学術雑誌）


• Analysis of neutralizing antibodies against hepatitis C virus in patients who were treated with pegylated-interferon plus ribavirin

  Mikiko Sasayama, Lin Deng, Soo Ryang Kim, Yoshi-Hiro Ide, Ikuo Shoji, Hak Hotta

  2, 2010年, Kobe Journal of Medical Sciences, 56(2) (2), E60 - E66, 英語

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Efficient production of infectious hepatitis C virus with adaptive mutations in cultured hepatoma cells

  Yasuaki Bungyoku, Ikuo Shoji, Tatsuhiko Makine, Tetsuya Adachi, Kazumi Hayashida, Motoko Nagano-Fujii, Yoshi-Hiro Ide, Lin Deng, Hak Hotta

  2009年07月, JOURNAL OF GENERAL VIROLOGY, 90(7) (7), 1681 - 1691, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Involvement of Creatine Kinase B in Hepatitis C Virus Genome Replication through Interaction with the Viral NS4A Protein

  Hiromichi Hara, Hideki Aizaki, Mami Matsuda, Fumiko Shinkai-Ouchi, Yasushi Inoue, Kyoko Murakami, Ikuo Shoji, Hayato Kawakami, Yoshiharu Matsuura, Michael M. C. Lai, Tatsuo Miyamura, Takaji Wakita, Tetsuro Suzuki

  2009年05月, JOURNAL OF VIROLOGY, 83(10) (10), 5137 - 5147, 英語

  [査読有り]

  研究論文（学術雑誌）


• HCV replication suppresses cellular glucose uptake through down-regulation of cell surface expression of glucose transporters

  Daisuke Kasai, Tetsuya Adachi, Lin Deng, Motoko Nagano-Fujii, Kiyonao Sada, Masanori Ikeda, Nobuyuki Kato, Yoshi-Hiro Ide, Ikuo Shoji, Hak Hotta

  2009年05月, JOURNAL OF HEPATOLOGY, 50(5) (5), 883 - 894, 英語

  [査読有り]

  研究論文（学術雑誌）


• Identification of Annexin A1 as a Novel Substrate for E6AP-Mediated Ubiquitylation

  Tetsu Shimoji, Kyoko Murakami, Yuichi Sugiyama, Mami Matsuda, Sachiko Inubushi, Junichi Nasu, Masayuki Shirakura, Tetsuro Suzuki, Takaji Wakita, Tatsuya Kishino, Hak Hotta, Tatsuo Miyamura, Ikuo Shoji

  2009年04月, JOURNAL OF CELLULAR BIOCHEMISTRY, 106(6) (6), 1123 - 1135, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Single-point mutations of the M protein of a measles virus variant obtained from a patient with subacute sclerosing panencephalitis critically affect solubility and subcellular localization of the M protein and cell-free virus production

  Da-Peng Jiang, Yoshi-Hiro Ide, Motoko Nagano-Fujii, Ikuo Shoji, Hak Hotta

  2009年04月, MICROBES AND INFECTION, 11(4) (4), 467 - 475, 英語

  [査読有り]

  研究論文（学術雑誌）


• Proteasomal Turnover of Hepatitis C Virus Core Protein Is Regulated by Two Distinct Mechanisms: a Ubiquitin-Dependent Mechanism and a Ubiquitin-Independent but PA28 gamma-Dependent Mechanism

  Ryosuke Suzuki, Kohji Moriishi, Kouichirou Fukuda, Masayuki Shirakura, Koji Ishii, Ikuo Shoji, Takaji Wakita, Tatsuo Miyamura, Yoshiharu Matsuura, Tetsuro Suzuki

  2009年03月, JOURNAL OF VIROLOGY, 83(5) (5), 2389 - 2392, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• A transgenic mouse line with a 58-kb fragment deletion in chromosome 11E1 that encompasses part of the Fam20a gene and its upstream region shows growth disorder

  Chunying An, Yoshi-Hiro Ide, Motoko Nagano-Fujii, Sohei Kitazawa, Ikuo Shoji, Hak Hotta

  4, 2009年, Kobe Journal of Medical Sciences, 55(4) (4), E82 - E92, 英語

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Double filtration plasmapheresis (DFPP) plus consecutive intravenous interferon (IFN)-β treatment for 4 weeks for non-sustained virological responders with genotype 1 b and high viral load previously treated with pegylated IFN plus ribavirin combination therapy - Focusing on early viral dynamics

  Ryang Kim Soo, Susumu Imoto, Keiji Mita, Miyuki Taniguchi, Ih Kim Ke, Ikuo Shouji, Motoko Nagano, Hak Hotta

  2009年, Acta Hepatologica Japonica, 50(8) (8), 470 - 472, 日本語

  [査読有り]

  研究論文（学術雑誌）


• Hepatitis C Virus Infection Induces Apoptosis through a Bax-Triggered, Mitochondrion-Mediated, Caspase 3-Dependent Pathway

  Lin Deng, Tetsuya Adachi, Kikumi Kitayama, Yasuaki Bungyoku, Sohei Kitazawa, Satoshi Ishido, Ikuo Shoji, Hak Hotta

  2008年11月, JOURNAL OF VIROLOGY, 82(21) (21), 10375 - 10385, 英語

  [査読有り]

  研究論文（学術雑誌）


• C型肝炎ウイルスコア蛋白質のユビキチン化シグナル

  勝二郁夫, 堀田博

  2008年11月, 日本生化学会大会・日本分子生物学会年会合同大会講演要旨集81回・31回, 巻, , pp. 2T20-5, 日本語

  研究論文（国際会議プロシーディングス）


• ペグインターフェロン リバビリン併用療法(併用療法)で急性膵炎を合併し、16週で中断したが、著効となった1b型高ウイルス量C型慢性肝炎の一症例

  勝二郁夫, 堀田博

  2008年10月, 肝臓, 49巻, Suppl.3, pp. A706-A706, 日本語

  研究論文（国際会議プロシーディングス）


• Virological characterization of the hepatitis C virus JFH-1 strain in lymphocytic cell lines

  Kyoko Murakami, Toshiro Kimura, Motonao Osaki, Koji Ishii, Tatsuo Miyamura, Tetsuro Suzuki, Takaji Wakita, Ikuo Shoji

  2008年07月, JOURNAL OF GENERAL VIROLOGY, 89(7) (7), 1587 - 1592, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• 非アルコール性脂肪性肝炎患者(NASH)における肝脂肪化、肝線維化に影響を及ぼす因子の検討 adipocytokinesを中心に

  堀田博, 勝二郁夫

  2008年04月, 肝臓, 49巻, Suppl.1, pp. A383-A383, 日本語

  研究論文（国際会議プロシーディングス）


• ペグインターフェロン/リバビリン併用療法におけるウイルス側のSVR予測因子の検討

  堀田博, 勝二郁夫

  2008年04月, 肝臓, 49巻, Suppl.1, pp. A213-A213(Supplement 1) (Supplement 1), 日本語

  研究論文（国際会議プロシーディングス）


• グルコーストランスポーターGLUT2の発現と肝臓グルコース取り込みにおけるC型肝炎ウイルスの影響に関する検討

  勝二郁夫, 堀田博

  2008年04月, 糖尿病, 51巻, Suppl.1, pp. S-196, 日本語

  研究論文（国際会議プロシーディングス）


• PEG-IFN リバビリン併用療法(併用療法)の治療効果予測におけるウイルスdynamicsの検討

  堀田博, 勝二郁夫

  2008年04月, 肝臓, 49巻, Suppl.1, pp. A313-A313, 日本語

  研究論文（国際会議プロシーディングス）


• Usefulness of a new immunoradiometric assay of HCV core antigen to predict virological response during PEG-IFN/RBV combination therapy for chronic hepatitis with high viral load of serum HCV RNA genotype 1b

  Noriko Sasase, Soo Ryang Kim, Ke Ih Kim, Miyuki Taniguchi, Susumu Imoto, Keiji Mita, Hak Hotta, Ikuo Shouji, Ahmed El-Shamy, Norifumi Kawada, Masatoshi Kudo, Yoshitake Hayashi

  2008年, INTERVIROLOGY, 51, 70 - 75, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Assemble and Interact: Pleiotropic Functions of the HCV Core Protein

  Polyak SJ, Klein KC, Shoji I, Miyamura T, Lingappa JR, Tan SL

  2006年, Hepatitis C Viruses: Genomes and Molecular Biology, 89-119, 国際誌, 国際共著している

  [査読有り]


• Outbreak of hepatitis C virus infection in an outpatient clinic

  T Ishikawa, Y Fukushima, Y Shiobara, T Kishimoto, S Tanno, Shoji, I, T Suzuki, T Matsui, Y Shimada, T Ohyama, R Nagai, T Miyamura

  2005年07月, JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 20(7) (7), 1087 - 1093, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• [Virion structure of hepatitis B virus].

  Shoji I

  2004年08月, Nihon rinsho. Japanese journal of clinical medicine, 62 Suppl 8, 8 - 11, 国内誌

  [招待有り]


• Role of the DExH motif of the Japanese encephalitis virus and hepatitis C virus NS3 proteins in the ATPase and RNA helicase activities

  A Utama, H Shimizu, F Hasebe, K Morita, A Igarashi, Shoji, I, Y Matsuura, M Hatsu, K Takamizawa, A Hagiwara, T Miyamura

  2000年08月, VIROLOGY, 273(2) (2), 316 - 324, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Identification of the canarypox virus thymidine kinase gene and insertion of foreign genes

  H Amano, S Morikawa, H Shimizu, Shoji, I, D Kurosawa, Y Matsuura, T Miyamura, Y Ueda

  1999年04月, VIROLOGY, 256(2) (2), 280 - 290, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Internal processing of hepatitis C virus NS3 protein

  Shoji, I, T Suzuki, M Sato, H Aizaki, T Chiba, Y Matsuura, T Miyamura

  1999年02月, VIROLOGY, 254(2) (2), 315 - 323, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Role of IQGAP1, a target of the small GTPases Cdc42 and Rac1, in regulation of E-cadherin-mediated cell-cell adhesion

  S Kuroda, M Fukata, M Nakagawa, K Fujii, T Nakamura, T Ookubo, Izawa, I, T Nagase, N Nomura, H Tani, Shoji, I, Y Matsuura, S Yonehara, K Kaibuchi

  1998年08月, SCIENCE, 281(5378) (5378), 832 - 835, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Efficient gene transfer into various mammalian cells, including non-hepatic cells, by baculovirus vectors

  Shoji, I, H Aizaki, H Tani, K Ishii, T Chiba, Saito, I, T Miyamura, Y Matsuura

  1997年10月, JOURNAL OF GENERAL VIROLOGY, 78(10) (10), 2657 - 2664, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Replication-deficient viral vectors for expression of HCV proteins in vitro and in vivo

  Y Matsuura, Shoji, I, Y Okada, H Aizaki, Y Aoki, H Tani, K Ishii, Saito, I, T Miyamura

  1997年, VACCINES 97 - MOLECULAR APPROACHES TO THE CONTROL OF INFECTIOUS DISEASES, 247 - 252, 英語, 国際誌

  [査読有り]

  研究論文（国際会議プロシーディングス）


• IN-VIVO AND IN-VITRO TRANS-CLEAVAGE ACTIVITY OF HEPATITIS-C VIRUS SERINE PROTEINASE EXPRESSED BY RECOMBINANT BACULOVIRUSES

  T SUZUKI, M SATO, S CHIEDA, SHOJI, I, T HARADA, Y YAMAKAWA, S WATABE, Y MATSUURA, T MIYAMURA

  1995年12月, JOURNAL OF GENERAL VIROLOGY, 76, 3021 - 3029, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Proteolytic activity of NS3 serine proteinase of hepatitis C virus efficiently expressed in Escherichia coli

  Shoji, I, T Suzuki, S Chieda, M Sato, T Harada, T Chiba, Y Matsuura, T Miyamura

  1995年12月, HEPATOLOGY, 22(6) (6), 1648 - 1655, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• KINETIC-ANALYSIS OF THE BINDING OF GUANINE-NUCLEOTIDE TO BOVINE BRAIN SMG-P25A

  SHOJI, I, A KIKUCHI, S KURODA, Y TAKAI

  1989年07月, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 162(1) (1), 273 - 281, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）

• インドネシアにおけるウマ様G3から典型的ヒトG1/G3へのロタウイルス遺伝子型の動的変化後に出現する異常なG9P[4]ロタウイルス【JST・京大機械翻訳】|||

  DINANA Zayyin, DINANA Zayyin, DOAN Yen Hai, MAHARANI Aussie Tahta, FITRIA Anisa Lailatul, YAMANI Laura Navika, YAMANI Laura Navika, JUNIASTUTI Juniastuti, SOETJIPTO Soetjipto, SOETJIPTO Soetjipto, MATSUI Chieko, DENG Lin, ABE Takayuki, TAKEMAE Nobuhiro, KAGEYAMA Tsutomu, KATAYAMA Kazuhiko, LUSIDA Maria Inge, LUSIDA Maria Inge, SHOJI Ikuo

  Inter-genogroup reassortment of Rotavirus A (RVA) strains has highlighted the spread of unusual RVA strains worldwide. We previously reported the equine-like G3 RVA as the predominant strain in Indonesia in 2015-2016. However, since July 2017, typical human genotypes G1 and G3 have replaced these strains completely. To understand how dynamic changes in RVA occur in Indonesia, we performed a detailed epidemiological study. A total of 356 stool specimens were collected from hospitalized children in Sidoarjo, Indonesia between 2018 and 2022. Whole-genome sequencing was performed for all 26 RVA-positive samples using next-generation sequencing. Twenty-four samples were determined to be the unusual RVA G9P[4], while two were G9P[6]. Detailed analysis revealed that seven G9P[4] strains had the typical DS-1-like backbone, while the other strains exhibited a double-reassortant profile (G9-N1) on the DS-1-like backbone. The Bayesian evolutionary analyses suggested that the Indonesian G9P[4] strains share a common ancestor with previously reported G9P[4] strains in the VP7 and VP4 genes. G9P[4] DS-1-like strains were identified as the predominant genotype in Indonesia in 2021 for the first time. These results suggest that the G9P[4] strains were generated from the previous G9P[4] strains that had undergone further intra-reassortments with the other circulating strains.

  2023年, 日本ウイルス学会学術集会プログラム・予稿集(Web), 70th(12) (12), e70106, 英語, 国際誌


• アジアとアフリカ諸国におけるロタウイルスワクチン導入後のロタウイルス株の遺伝子型配置の分布の変化

  DOAN Yen Hai, TAKEMAE Nobuhiro, SUZUKI Toshihiko, DENNIS Francis Ekow, ARMAH George Enyimah, UTSUMI Takako, SHOJI Ikuo, YAMANI Laura Navika, LUSIDA Maria Inge, MIYOSHI Shinichi, SARKAR Mamta Chawla, HAGA Kei, FUJII Yoshiki, SHIMIZU Hiroyuki, OKA Tomoichiro, MURAMATSU Masamichi, KAGEYAMA Tsutomu, KATAYAMA Kazuhiko

  2022年, 日本ウイルス学会学術集会プログラム・予稿集(Web), 69th


• B型肝炎ウイルスcccDNAの生成は抗腫瘍薬ミトキサントロンにより促進される

  堀田博, 堀田博, 西本幸子, とう琳, 靭千恵, 勝二郁夫, 脇田隆字, 村松正道

  2021年, 日本ウイルス学会学術集会プログラム・予稿集(Web), 68th


• 細胞内アネキシン5はC型肝炎ウイルスの増殖抑制に関与する

  阿部隆之, 松井千絵子, DENG Lin, 松浦善治, 勝二郁夫

  2020年, 日本分子生物学会年会プログラム・要旨集(Web), 43rd


• HCV NS3/4AプロテアーゼはSPG20を選択的に切断し脂肪滴の巨大化を促進する

  松井千絵子, YULIANDARI Putu, DENG Lin, 阿部隆之, 勝二郁夫

  2020年, 日本分子生物学会年会プログラム・要旨集(Web), 43rd


• HCV NS3/4AプロテアーゼはSPG20を選択的に切断し脂肪滴の巨大化を促進する

  松井千絵子, PUTU Yuliandari, LIN Deng, 阿部隆之, 勝二郁夫

  2019年, 日本ウイルス学会学術集会プログラム・予稿集(Web), 67th


• C型肝炎ウイルスNS5A蛋白質のISGylation修飾反応におけるウイルス遺伝子型間の解析

  阿部隆之, 松井千絵子, LIN Deng, 福原崇介, 松浦善治, 勝二郁夫

  2019年, 日本ウイルス学会学術集会プログラム・予稿集(Web), 67th


• 脱ユビキチン化酵素USP15阻害剤候補分子の機能解析

  勝二郁夫, 松井千絵子, DENG Lin, 阿部隆之

  2017年, 日本生化学会大会(Web), 90th


• 脱ユビキチン化酵素USP15阻害剤の探索と機能解析

  勝二郁夫, DENG Lin, 松井千絵子, 南奈苗, 阿部隆之

  2016年, 日本分子生物学会年会プログラム・要旨集(Web), 39th


• C型肝炎ウイルスによる糖代謝異常

  勝二 郁夫, 鄧 琳, 松井 千絵子, 堀田 博

  日本ウィルス学会, 2015年12月, ウイルス, 65(2) (2), 263 - 268, 日本語

  [査読有り][招待有り]

  記事・総説・解説・論説等（学術雑誌）


• C型肝炎ウイルス感染によるHepatocyte nuclear factor(HNF)-1α蛋白質の選択的分解機構

  松井千絵子, 勝二郁夫, SIANIPAR Imelda Rosalyn, 南奈苗, DENG Lin, 堀田博

  2014年, 日本ウイルス学会学術集会プログラム・抄録集, 62nd


• C型肝炎ウイルスによるHNF-1α蛋白質の選択的分解機構の解析

  勝二郁夫, 松井千絵子, SIANIPAR Imelda Rosalyn, 南奈苗, DENG Lin, 堀田博

  2014年, 日本分子生物学会年会プログラム・要旨集(Web), 37th


• HCV NS5AとHepatocyte nuclear factor(HNF)-1αの相互作用と病態生理

  松井千絵子, 勝二郁夫, 南奈苗, SIANIPAR Imelda Rosalyn, DENG Lin, 堀田博

  2013年, 日本ウイルス学会学術集会プログラム・抄録集, 61st


• HCV感染による糖代謝障害の分子機序

  勝二郁夫, 松井千絵子, LIN Deng, 堀田博

  2013年, 日本ウイルス学会学術集会プログラム・抄録集, 61st


• C型肝炎ウイルスNS5AはB細胞のチロシンキナーゼFynを活性化する

  中島謙治, 竹内健二, 千原一泰, 堀口朋子, 孫雪東, DENG Lin, 勝二郁夫, 堀田博, 定清直

  2012年10月31日, 日本ウイルス学会学術集会プログラム・抄録集, 60th, 244, 日本語


• プロテアーゼ阻害薬併用時代でのPEG-IFNα-2a/Ribavirin療法の位置付け

  瀬尾靖, 矢野嘉彦, 三木章, 勝二郁夫, 堀田博, 東健

  2012年09月, 肝臓, 53(Suppl.2) (Suppl.2), A690, 日本語

  [査読有り]

  会議報告等


• C型肝炎ウイルスによるGLUT2遺伝子発現抑制の分子機構

  松井千絵子, 勝二郁夫, DENG Lin, 堀田博

  2012年, 日本ウイルス学会学術集会プログラム・抄録集, 60th


• C型肝炎ウイルス感染はHNF-1αの発現を負に制御しGLUT2遺伝子発現を抑制する

  勝二郁夫, 松井千絵子, 兼田祟作, IMELDA Rosalyn Sianipar, DENG Lin, 堀田博

  2012年, 日本分子生物学会年会プログラム・要旨集(Web), 35th


• C型肝炎ウイルスNS5A蛋白質のSrc homology2/3ドメイン結合能とB細胞での発現によるSrcファミリーキナーゼFynの活性化

  中島謙治, 竹内健司, 千原一泰, 堀口朋子, SUN Xuedong, LIN Deng, 勝二郁夫, 堀田博, 定清直

  2012年, 日本分子生物学会年会プログラム・要旨集(Web), 35th, 1LBA-0769 (WEB ONLY), 日本語


• 【C型肝炎-最新治療コンセンサス】 NS5A-IRRDR変異数

  勝二郁夫, 堀田博

  2011年12月, 医学のあゆみ, 239巻, 12-13, pp. 1208-1211, 日本語

  記事・総説・解説・論説等（学術雑誌）


• 【C型肝炎のすべて2012】 インターフェロン治療の分子基盤 C型肝炎ウイルスNS5A領域のISDR・IRRDRとインターフェロン治療効果予測

  勝二郁夫, 堀田博

  2011年12月, 肝・胆・膵, 63巻, 6号, pp. 1063-1069, 日本語

  記事・総説・解説・論説等（学術雑誌）


• SEQUENCE HETEROGENEITY OF NS5A OF HCV GENOTYPES 2A AND 2B AFFECTS RVR AND SVR TO PEG-IFN/RBV COMBINATION THERAPY

  H. Hotta, A. El-Shamy, S. R. Kim, S. Imoto, C. Aoki, Y. Ide, I. Shoji

  2010年, JOURNAL OF HEPATOLOGY, 52, S111 - S111, 英語

  研究発表ペーパー・要旨（国際会議）


• THE HNRNP H1 MODULATES PRODUCTION OF HCV PARTICLES THROUGH INTERACTION WITH HCV CORE PROTEIN AND HCV IRES RNA

  Ikuo Shoji, Hak Hotta

  2009年10月, HEPATOLOGY, 50(4) (4), 960A - 961A, 英語

  研究発表ペーパー・要旨（国際会議）


• C型肝炎ウイルス感染によるインスリン抵抗性誘導の分子機序について

  井出良浩, 兼田崇作, 犬伏祥子, 足達哲也, LIN Deng, 勝二郁夫, 堀田博

  2009年, 日本ウイルス学会学術集会プログラム・抄録集, 57th


• C型肝炎ウイルスコア蛋白質の安定性調節因子E6AP及びPA28γの相互作用解析

  山下亮輔, 福田浩一郎, 犬伏祥子, 村上恭子, 鈴木哲朗, 森石恆司, 松浦善治, DENG Lin, 井出良浩, 堀田博, 勝二郁夫

  2009年, 日本分子生物学会年会講演要旨集, 32nd(Vol.1) (Vol.1)


• Virological characterization of the hepatitis C virus JFH-1 strain in lymphocytic cell lines

  Kyoko Murakami, Toshiro Kimura, Motonao Osaki, Koji Ishii, Tatsuo Miyamura, Tetsuro Suzuki, Takaji Wakita, Ikuo Shoji

  2008年07月, JOURNAL OF GENERAL VIROLOGY, 89, 1587 - 1592, 英語


• 1b型高ウイルス量高齢者C型慢性肝炎に対するPEG IFNα-2b/リバビリン治療(併用療法)の検討

  金 守良, 井本 勉, 婦木 秀一, 金 啓二, 谷口 美幸, 長野 基子, 堀田 博, 勝二 郁夫, 寒原 芳浩, 前川 陽子, 工藤 正俊, 林 祥剛

  1b型高ウイルスC型慢性肝炎の65歳以上（高齢群）23名（平均年齢69.4歳）と65歳未満（非高齢群）52名（平均年齢53.5歳）を対象にIFNα2b/リバビリン併用療法を比較検討した．著効率と中断率は高齢群37.5%（6/16），30.4%（7/23），非高齢群50%（20/40），23.1%（12/52）で有意差はなく，HCVコア抗原減少率，2-5AS応答率も両群間に有意差を認めなかった．高齢群では著効例は非著効例に比して開始時のAFP値が有意に低値であった（P<0.01）．高齢群では著効・非著効を問わず治療前後でAFP値は有意に低下しており（開始時10.1±9.55 ng/ml，終了時5.18±4.52 ng/ml（P<0.05）），治療により発癌抑制がもたらされた可能性が考えられた．よって，高齢群においては，たとえ著効に至らない場合であっても治療の完遂が重要である．

  一般社団法人 日本肝臓学会, 2008年04月25日, 肝臓 = ACTA HEPATOLOGICA JAPONICA, 49(4) (4), 145 - 152, 日本語


• Dynamic behavior of hepatitis C virus quasispecies in a long-term culture of the three-dimensional radial-flow bioreactor system.

  Kyoko Murakami, Yasushi Inoue, Su-Su Hmwe, Kazuhiko Omata, Tomokatsu Hongo, Koji Ishii, Sayaka Yoshizaki, Hideki Aizaki, Tomokazu Matsuura, Ikuo Shoji, Tatsuo Miyamura, Tetsuro Suzuki

  Hepatitis C virus (HCV) exists in infected individuals as quasispecies, usually consisting of a dominant viral isolate and a variable mixture of related, yet genetically distinct, variants. A prior HCV infection system was developed using human hepatocellular carcinoma cells cultured in the three-dimensional radial-flow bioreactor (RFB), in which the cells retain morphological appearance and their differentiated hepatocyte functions for an extended period of time. This report studies the selection and alteration of the viral quasispecies in the RFB system inoculated with pooled serum derived from HCV carriers. Monitoring the viral RNA and core protein in the culture supernatants, together with nucleotide sequencing of hypervariable region 1 of the HCV genome, demonstrated that (1) the virus production intermittently fluctuated in the cultures, (2) the viral genetic diversity was markedly reduced 3 days post-infection (p.i.), and (3) dominant species changed on days 19-33p.i., suggesting that the virus populations can be selected according to susceptibility to the viral infection and replication. A therapeutic effect of interferon-alpha also demonstrated the inhibition of HCV expression. Thus, this HCV infection model in the RFB system should be useful for investigating the dynamic behavior of HCV quasispecies in cultured cells and evaluating anti-HCV compounds.

  2008年03月, Journal of virological methods, 148(1-2) (1-2), 174 - 81, 英語, 国際誌

  [査読有り]


• Dynamic behavior of hepatitis C virus quasispecies in a long-term culture of the three-dimensional radial-flow bioreactor system

  Kyoko Murakami, Yasushi Inoue, Su-Su Hmwe, Kazuhiko Omata, Tomokatsu Hongo, Koji Ishii, Sayaka Yoshizaki, Hideki Aizaki, Tornokazu Matsuura, Ikuo Shoji, Tatsuo Miyamura, Tetsuro Suzuki

  2008年03月, JOURNAL OF VIROLOGICAL METHODS, 148(1-2) (1-2), 174 - 181, 英語


• Dynamic behavior of hepatitis C virus quasispecies in a long-term culture of the three-dimensional radial-flow bioreactor system

  Kyoko Murakami, Yasushi Inoue, Su-Su Hmwe, Kazuhiko Omata, Tomokatsu Hongo, Koji Ishii, Sayaka Yoshizaki, Hideki Aizaki, Tornokazu Matsuura, Ikuo Shoji, Tatsuo Miyamura, Tetsuro Suzuki

  2008年03月, JOURNAL OF VIROLOGICAL METHODS, 148(1-2) (1-2), 174 - 181, 英語


• ペグインターフェロン/リバビリン併用療法におけるHCV CoreおよびNS5Aの多様性によるSVR予測因子とNon-SVR予測因子の検討

  エルシャーミ アーメド, 足達哲也, 犬伏祥子, 勝二郁夫, 堀田博

  2008年, 日本ウイルス学会学術集会プログラム・抄録集, 56th


• Molecular determinants of E6AP-dependent degradation of hepatitis C virus core protein

  Ikyo Shoji, Kyoko Murakami, Kouichirou Fukuda, Motonao Osaki, Tetsuro Suzu, Tatsuo Miyamura, Takaji Wakita

  2007年10月, HEPATOLOGY, 46(4) (4), 451A - 451A, 英語

  研究発表ペーパー・要旨（国際会議）


• Molecular biology of hepatitis C virus.

  Tetsuro Suzuki, Hideki Aizaki, Kyoko Murakami, Ikuo Shoji, Takaji Wakita

  Infection with hepatitis C virus (HCV), which is distributed worldwide, often becomes persistent, causing chronic hepatitis, cirrhosis, and hepatocellular carcinoma. For many years, the characterization of the HCV genome and its products has been done by heterologous expression systems because of the lack of a productive cell culture system. The development of the HCV replicon system is a highlight of HCV research and has allowed examination of the viral RNA replication in cell culture. Recently, a robust system for production of recombinant infectious HCV has been established, and classical virological techniques are now able to be applied to HCV. This development of reverse genetics-based experimental tools in HCV research can bring a greater understanding of the viral life cycle and pathogenesis of HCV-induced diseases. This review summarizes the current knowledge of cell culture systems for HCV research and recent advances in the investigation of the molecular virology of HCV.

  2007年06月, Journal of gastroenterology, 42(6) (6), 411 - 23, 英語, 国内誌

  [査読有り]


• Molecular biology of hepatitis C virus

  Tersuro Suzuki, Hideki Aizaki, Kyoko Murakami, Ikuo Shoji, Takaji Wakita

  2007年06月, JOURNAL OF GASTROENTEROLOGY, 42(6) (6), 411 - 423, 英語

  書評論文,書評,文献紹介等


• E6AP ubiquitin ligase mediates ubiquitylation and degradation of hepatitis C virus core protein

  Masayuki Shirakura, Kyoko Murakami, Tohru Ichimura, Ryosuke Suzuki, Tetsu Shimoji, Kouichirou Fukuda, Katsutoshi Abe, Shigeko Sato, Masayoshi Fukasawa, Yoshio Yamakawa, Masahiro Nishijima, Kohji Moriishi, Yoshiharu Matsuura, Takaji Wakita, Tetsuro Suzuki, Peter M. Howley, Tatsuo Miyamura, Ikuo Shoji

  2007年02月, JOURNAL OF VIROLOGY, 81(3) (3), 1174 - 1185, 英語


• E6AP ubiquitin ligase mediates ubiquitylation and degradation of hepatitis C virus core protein.

  Masayuki Shirakura, Kyoko Murakami, Tohru Ichimura, Ryosuke Suzuki, Tetsu Shimoji, Kouichirou Fukuda, Katsutoshi Abe, Shigeko Sato, Masayoshi Fukasawa, Yoshio Yamakawa, Masahiro Nishijima, Kohji Moriishi, Yoshiharu Matsuura, Takaji Wakita, Tetsuro Suzuki, Peter M Howley, Tatsuo Miyamura, Ikuo Shoji

  Hepatitis C virus (HCV) core protein is a major component of viral nucleocapsid and a multifunctional protein involved in viral pathogenesis and hepatocarcinogenesis. We previously showed that the HCV core protein is degraded through the ubiquitin-proteasome pathway. However, the molecular machinery for core ubiquitylation is unknown. Using tandem affinity purification, we identified the ubiquitin ligase E6AP as an HCV core-binding protein. E6AP was found to bind to the core protein in vitro and in vivo and promote its degradation in hepatic and nonhepatic cells. Knockdown of endogenous E6AP by RNA interference increased the HCV core protein level. In vitro and in vivo ubiquitylation assays showed that E6AP promotes ubiquitylation of the core protein. Exogenous expression of E6AP decreased intracellular core protein levels and supernatant HCV infectivity titers in the HCV JFH1-infected Huh-7 cells. Furthermore, knockdown of endogenous E6AP by RNA interference increased intracellular core protein levels and supernatant HCV infectivity titers in the HCV JFH1-infected cells. Taken together, our results provide evidence that E6AP mediates ubiquitylation and degradation of HCV core protein. We propose that the E6AP-mediated ubiquitin-proteasome pathway may affect the production of HCV particles through controlling the amounts of viral nucleocapsid protein.

  2007年02月, Journal of virology, 81(3) (3), 1174 - 85, 英語, 国際誌

  [査読有り]


• HCVコア蛋白と結合する新規宿主因子hnRNPH1/H2の同定と相互作用解析

  2007年


• 血球系細胞におけるHCV JFH-1株の感染および複製の検討

  2007年


• Virological characterization of HCV JFH-1 strain in B-lymphocytes.

  2007年


• Virological characterization of HCV JFH-1 strain in B-lymphocytes.

  2007年


• Production of infectious hepatitis C virus particles in three-dimensional cultures of the cell line carrying the genome-length dicistronic viral RNA of genotype 1b.

  Kyoko Murakami, Koji Ishii, Yousuke Ishihara, Sayaka Yoshizaki, Keiko Tanaka, Yasufumi Gotoh, Hideki Aizaki, Michinori Kohara, Hiroshi Yoshioka, Yuichi Mori, Noboru Manabe, Ikuo Shoji, Tetsutaro Sata, Ralf Bartenschlager, Yoshiharu Matsuura, Tatsuo Miyamura, Tetsuro Suzuki

  We show that a dicistronic hepatitis C virus (HCV) genome of genotype 1b supports the production and secretion of infectious HCV particles in two independent three-dimensional (3D) culture systems, the radial-flow bioreactor and the thermoreversible gelation polymer (TGP), but not in monolayer cultures. Immunoreactive enveloped particles, which are 50-60 nm in diameter and are surrounded by membrane-like structures, are observed in the culture medium as well as at the endoplasmic reticulum membranes and in dilated cytoplasmic cisternae in spheroids of Huh-7 cells. Infection of HCV particles is neutralized by anti-E2 antibody or patient sera that interfere with E2 binding to human cells. Finally, the utility of the 3D-TGP culture system for the evaluation of antiviral drugs is shown. We conclude that the replicon-based 3D culture system allows the production of infectious HCV particles. This system is a valuable tool in studies of HCV morphogenesis in a natural host cell environment.

  2006年08月01日, Virology, 351(2) (2), 381 - 92, 英語, 国際誌

  [査読有り]


• E6-associated protein mediates ubiquitylation and degradation of hepatitis C virus core protein

  I. Shoji, M. Shirakura, T. Ichimura, K. Murakami, T. Shimoji, R. Suzuki, T. Suzuki, K. Fukuda, S. Sato, M. Fukasawa, Y. Yamakawa, M. Nishijima, T. Miyamura

  2006年07月, JOURNAL OF CLINICAL VIROLOGY, 36, S26 - S26, 英語

  研究発表ペーパー・要旨（国際会議）


• Role of chaperonin-containing TCP complex (CCT) and heat shock cognate protein 70 (Hsc70) in the HCV RNA replication

  T. Suzuki, Y. Inoue, H. Aizaki, M. Matsuda, M. Shirakura, K. Murakami, I. Shoji, Y. Matsuura, T. Miyamura

  2006年07月, JOURNAL OF CLINICAL VIROLOGY, 36, S112 - S113, 英語

  研究発表ペーパー・要旨（国際会議）


• Proteomic profiling of lipid droplet proteins in hepatoma cell lines expressing hepatitis C virus core protein.

  Shigeko Sato, Masayoshi Fukasawa, Yoshio Yamakawa, Tohru Natsume, Tetsuro Suzuki, Ikuo Shoji, Hideki Aizaki, Tatsuo Miyamura, Masahiro Nishijima

  Hepatitis C virus (HCV) core protein has been suggested to play crucial roles in the pathogeneses of liver steatosis and hepatocellular carcinomas due to HCV infection. Intracellular HCV core protein is localized mainly in lipid droplets, in which the core protein should exert its significant biological/pathological functions. In this study, we performed comparative proteomic analysis of lipid droplet proteins in core-expressing and non-expressing hepatoma cell lines. We identified 38 proteins in the lipid droplet fraction of core-expressing (Hep39) cells and 30 proteins in that of non-expressing (Hepswx) cells by 1-D-SDS-PAGE/MALDI-TOF mass spectrometry (MS) or direct nanoflow liquid chromatography-MS/MS. Interestingly, the lipid droplet fraction of Hep39 cells had an apparently lower content of adipose differentiation-related protein and a much higher content of TIP47 than that of Hepswx cells, suggesting the participation of the core protein in lipid droplet biogenesis in HCV-infected cells. Another distinct feature is that proteins involved in RNA metabolism, particularly DEAD box protein 1 and DEAD box protein 3, were detected in the lipid droplet fraction of Hep39 cells. These results suggest that lipid droplets containing HCV core protein may participate in the RNA metabolism of the host and/or HCV, affecting the pathopoiesis and/or virus replication/production in HCV-infected cells.

  2006年05月, Journal of biochemistry, 139(5) (5), 921 - 30, 英語, 国際誌

  [査読有り]


• Pleiotropic Functions of the HCV Core Protein.

  2006年, Hepatitis C Viruses: Genomes and Molecular Biology, 89-119


• Cdc42 and Rac1 regulate the interaction of IQGAP1 with beta-catenin

  M Fukata, S Kuroda, M Nakagawa, A Kawajiri, N Itoh, Shoji, I, Y Matsuura, S Yonehara, H Fujisawa, A Kikuchi, K Kaibuchi

  1999年09月, JOURNAL OF BIOLOGICAL CHEMISTRY, 274(37) (37), 26044 - 26050, 英語


• バキュロウイルスを用いた哺乳動物細胞への遺伝子導入とその応用

  松浦 善治, 勝二 郁夫, 葉 真珠, 谷 英樹, 石井 孝司, 宮村 達男

  日本ウィルス学会, 1997年12月01日, ウイルス, 47(2) (2), 247 - 256, 日本語


• Regulation of cross-linking of actin filament by IQGAP1, a target for Cdc42

  M Fukata, S Kuroda, K Fujii, T Nakamura, Shoji, I, Y Matsuura, K Okawa, A Iwamatsu, A Kikuchi, K Kaibuchi

  1997年11月, JOURNAL OF BIOLOGICAL CHEMISTRY, 272(47) (47), 29579 - 29583, 英語


• バキュロウイルスをベクターとしたほ乳動物細胞における組換え蛋白の発現

  青木博史, 迫田義博, 土屋佳紀, 勝二郁夫, 松浦善治, 高田礼人, 喜田宏, 杉山公宏, 福所秋雄

  1997年03月, 日本獣医学会学術集会講演要旨集, 123rd, 153, 日本語


• Expression and purification of hepatitis C virus serine proteinase

  I. Shoji, T. Suzuki, M. Sato, Y. Matsuura, T. Miyamura

  1995年09月, Nippon rinsho. Japanese journal of clinical medicine, 53 Suppl, 30 - 35

  書評論文,書評,文献紹介等


• ras p21類似GTP結合蛋白質smg p25Aの新しい調節蛋白質の精製と性状

  荒木伸, 菊池章, 佐々木卓也, 畑裕, 磯村光男, 勝二郁夫, 黒田真也, 高井義美

  1989年, 神経化学, 28(1) (1), 82 - 83, 日本語

• 日本癌学会


• 日本消化器病学会


• アメリカ微生物学会


• 日本分子生物学会


• 日本内科学会


• 日本肝臓学会


• 日本ウイルス学会

• C型肝炎ウイルスによる脂肪滴肥大化維持の分子機構とウイルス学的意義の解明

  勝二 郁夫

  日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 2020年04月01日 - 2023年03月31日

  HCV感染患者の肝に脂肪化が発症することは臨床上よく知られ、HCV感染による脂質代謝系の変化が詳しく解析されてきた。しかし、なぜHCV感染初期に肝細胞で脂肪滴が肥大化し、肥大脂肪滴が維持されるのかの分子機構は全く分かっていない。本研究では、C型肝炎ウイルス(HCV）感染による肝細胞での脂肪滴肥大化維持の分子機構の解明を目的とした。さらにHCV感染による肝細胞での脂肪滴の肥大化を抑制する方法を開発し、肝脂肪化の抑制法とHCV増殖の抑制法の開発のための分子基盤の構築を目指す。具体的には以下の３点について解析を行う。1) 脂肪滴肥大化維持に必要なウイルス因子および宿主因子の同定、2) 脂肪滴肥大化維持に必要な分子機構の解明、3) 脂肪滴肥大化抑制法の開発。研究方法はHCV感染培養系、HCV RNAレプリコン系、プラスミド発現系を用い、HCV NS3/4Aプロテアーゼによる脂肪滴調節因子SPG20の切断とアディポフィリン(ADRP)量の変化と脂肪滴肥大化の維持の関連について解析する。さらにDAA製剤などの薬剤による脂肪滴縮小効果を解析する。 本年度の結果は以下の通りである。1. HCV感染によるJNK活性化とAIP4のリン酸化および活性型変換の解析. 2. HCV感染によるE3リガーゼAIP4によるADRPユビキチン化および発現量の解析. 3. 脂肪滴周囲蛋白質（SPG20, TIP47, ADRP）およびユビキチンリガーゼAIP4によるADRPユビキチン化機構の解析 を行った。その結果、HCV JNK活性化によりAIP4のリン酸化、活性化が引き起こされること、ADRPがユビキチン化を受け蛋白質量が減少すること、しかし、脂肪滴周囲のADRP量は減少しないことを明らかにした。


• グローバル・ウェルフェアの実現と課題をめぐる文理協働型実証研究

  桜井 徹, 太田 和宏, 杉下 智彦, 大月 一弘, 辛島 理人, 工藤 晴子, 中澤 港, 勝二 郁夫, 新川 匠郎, 青山 薫, 梅屋 潔, 小川 啓一, 齋藤 剛, 益田 岳, クラクストン ジェームズ

  日本学術振興会, 科学研究費助成事業, 基盤研究(B), 神戸大学, 2019年04月01日 - 2023年03月31日

  本研究は、以下の3つの切り口から文理協働による共同研究の遂行を目的としている。第一に、移民・難民の起源地における住民の基本的な生活条件を直視することを通して、大規模な移民現象のプッシュ要因を文理両面から総合的に再検討する。第二に、多領域横断的な研究体制を構築し、必然的に文理融合的な様相を呈する移民・難民の起源地の生活条件の問題に、学際的なチームが協力して打開策を検討する。第三に、開発援助が実施されている地域に実際に生きる人々／それらの地域を故郷とする人々が、様々な援助をどのように受け止め、また将来に向けていかに活かせるのかを分析する。 残念ながらコロナ禍の影響によって、イスラム圏から来た在日外国人の聞き取り調査など国内での調査研究は実施することができたものの、ホンジュラス、南アフリカ、モロッコ、ケニア、イラン、キルギスタン、インドネシア、フィリピン等の国々を対象に、医学、社会学、法学、人類学、教育学、政治経済学等の多様な角度から現地調査を遂行し、どのような開発援助の問題点が現地で明らかとなっているのかを分析するという目的は果たせなかった。 しかしながら、この間、インドネシアのアイルランガ大学や南アフリカのケープタウン大学をはじめとする海外の研究者や世界銀行、ユネスコ、ユニセフとは、海外共同調査やワークショップ開催に向けて定期的にコンタクトを取り続け、海外調査や研究集会を再開するための準備を着々と進めることができた。


• C型肝炎ウイルスの脂肪滴形成機構

  勝二 郁夫

  日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 2014年04月01日 - 2017年03月31日

  (1)HCVcc感染Huh-7.5細胞でSPG20が切断される。(2)HCV NS3/4Aを一過性にhuh-7細胞に発現させるとSPG20が切断される。(3)不活化型NS3/4Aを発現させてもSPG20は切断されない。(4)NS3/4A阻害剤でSPG20の切断が抑制されるが、NS5A阻害剤では変化がなかった。(5)HCVcc感染細胞Huh-7.5にNS3/4A阻害剤を投与すると脂肪滴の大きさも縮小した。以上よりHCV感染細胞においてはNS3/4AプロテアーゼがSPG20を切断し、脂肪滴の巨大化を促進することが示された。


• Ｃ型肝炎ウイルスによる糖代謝異常の分子機序の解明

  堀田 博, 勝二 郁夫, デン リン

  日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 2012年04月01日 - 2015年03月31日

  HCVによる糖新生亢進に関与する転写因子FoxO1の持続的活性化の制御機構及びアポトーシス誘導シグナル伝達への影響並びに酸化ストレスやJNK活性化との関連の解明を目的とした。その結果、HCV感染により、酸化ストレス（活性酸素種[ROS]産生）→JNK活性化→脱リン酸化酵素MKP3の発現亢進→FoxO1脱リン酸化（活性化）→FoxO1核内蓄積（FoxO1転写活性の亢進）→PEPCK及びG6Pase遺伝子の転写促進を介して、糖新生が亢進することが示された。また、酸化ストレス→JNK活性化→Bim発現亢進→Bax活性化を介してミトコンドリア依存性アポトーシスが誘導されることが示された。


• C 型肝炎ウイルス産生調節機構の研究

  勝二 郁夫, 井出 良浩

  日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 2010年 - 2012年

  C型肝炎ウイルス(HCV)のウイルス産生調節機構はHCV RNAレプリコン細胞やJFH1株を用いたウイルス産生系の進歩により、HCV生活環とウイルス増殖に必要な宿主因子の解析が可能となってきた。本研究ではHCV産生の分子機序を明らかにするために、HCV蛋白質と結合する宿主因子とその生理学的意義を解析した。まず、HCVコア蛋白質と結合する宿主因子hnRNPH1/H2/FとRNA結合の重要性について解析した。HCV RNAを添加したところ、コア蛋白質とhnRNPHの結合が阻害され、RNaseを添加すると結合が回復したことから、両者の結合にRNAが重要であると考えられた。hnRNPFにおいても同様の現象を認めた。この二つの因子が協調してウイルス産生を制御していることが示唆された。また、HCV NS5A蛋白質の新規結合因子として細胞内のユビキチンリガーゼp138、転写因子HNF-1a、ヒストンメチル基転移酵素SMYD3などを同定した。p138はHCVのNS5A蛋白質と相互作用するが、他のHCV蛋白質との相互作用は認められず、NS5A特異的な結合と考えられた。p138はNS5Aをユビキチン依存性に分解を促進し、ウイルス複製を制御することが示唆された。NS5A蛋白質とp138の結合部位を各々の欠損変異体を作製してマッピングを行った。両者の結合に重要な領域を同定するためには、更に欠損変異体を作製して詳細に解析する必要がある。また、NS5Aのユビキチン化部位を決定するために13種の点変異体を作製し解析を行い、複数箇所のユビキチン化部位を同定した。これらの研究はHCVの生活環と病原性の理解に貢献するものと考えられた。


• C型肝炎ウイルスの増殖適応変異と病原性の研究

  堀田 博, 勝二 郁夫, 足達 哲也, 定 清直, 長野 基子

  日本学術振興会, 科学研究費助成事業, 特定領域研究, 神戸大学, 2007年 - 2008年

  HCV J6/JFH-1株をHuh-7.5細胞で27、38、47代継代したウイルス株(P-27、P-38、P-47)は、親株に比べて50〜300倍高い感染性ウイルス粒子産生能を示した。P-27には8ヵ所(E2に4ヵ所、NS2に2ヵ所、NS5AとNS5Bに1ヵ所ずつ)のアミノ酸変異がみられ、P-38では上記8ヵ所に加えてCoreに1ヵ所、P-47では更に5'-UTRとNS5Bに1ヵ所ずつの変異がみられた。reverse genetics法により親株にP-27で見られた8ヵ所の変異をすべて導入すると感染性ウイルス粒子産生能が約10倍増加することを確認した。しかし、7ヵ所以下の部分的変異導入では感染性ウイルス粒子産生能の有意な増加は観察されなかった。P-27は親株に比べて抗CD81抗体による吸着阻害を受けにくく、その性質はE2の単一変異(N534H)によるものであった。この変異によるE2の糖鎖付加の欠失が、ウイルスレセプターとの相互作用に影響を及ぼして、HCVの感染効率を増加させている可能性が考えられた。さらに、P-27ではウイルス遺伝子複製能とウイルスタンパク質合成能が親株に比べて軽度増加していた。このような複数の変異が複合的に作用して顕著な感染性ウイルス粒子産生能の増加をもたらしたものと考えられた。 また、HCV感染細胞と非感染細胞を用いてプロテオーム解析を行い、感染の持続に伴って発現が減少する宿主タンパク質として、FABP1を同定した。FABP1は脂肪酸取込みに重要な役割を果たしているが、HCV感染によるFABP1発現の低下が、細胞の脂質代謝等にどのように影響を及ぼしているかについて、現在解析を進めている。同様に、肝細胞への糖取込みに重要な役割を果たしているGLUT2の発現がHCV複製により抑制されることも明らかにした。mRNA定量やルシフェラーゼレポーターを用いたプロモーターアッセイにより、GLUT2発現の抑制が転写レベルでおこっていること、及び肝細胞において重要な転写因子HNF1αが関与することを明らかにした。HCVが肝細胞の糖・脂質代謝異常を引き起こす分子機序を考える上で興味ある知見である。