Research activity information

• 2023 (公財)ウイルス肝炎研究財団, 令和４年度肝炎に関する研究助成事業「研究奨励金」, 選択的蛋白質分解機構を介した HCV誘導性病原発現機構の解明


• 2017 第5回 神緑会 Young Investigator Award 優秀賞


• 2015 第3回 神緑会 Young Investigator Award 特別賞


• 2013 神戸大学医学部優秀学術論文賞


• 2013 第1回 神緑会 Young Investigator Award 優秀賞

• 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.

  Dec. 2024, Journal of medical virology, 96(12) (12), e70106, English, International magazine

  Scientific journal


• 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.

  Sep. 2024, Journal of virology, 98(9) (9), e0085524, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 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.

  Dec. 2023, Viruses, 15(12) (12), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 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.

  Oct. 2023, Journal of virology, 97(10) (10), e0128723, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 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.

  Oct. 2023, Journal of medical virology, 95(10) (10), e29164, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 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.

  Aug. 2023, The Kobe journal of medical sciences, 69(3) (3), E86-E95, English, Domestic magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 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.

  Jun. 2023, Journal of virology, 97(6) (6), e0065523, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 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.

  Jan. 2023, Journal of medical virology, 95(2) (2), e28485, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 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, Jul. 2022, Autophagy Reports, 1(1) (1), 264 - 285

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Hepatitis C virus (HCV)-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 still remain unclear. We sought to identify a novel role of 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 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 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. Co-immunoprecipitation 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 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 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 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.

  Jan. 2022, Journal of virology, 96(6) (6), JVI0181121, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 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.

  Oct. 2021, The Journal of general virology, 102(10) (10), English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 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.

  Sep. 2021, The Kobe journal of medical sciences, 67(2) (2), E38-E47, English, Domestic magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 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.

  Mar. 2021, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 88, 104703 - 104703, English, International magazine, Co-authored internationally

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 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, Frontiers in cellular and infection microbiology, 11, 796664 - 796664, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• ISGylation of Hepatitis C Virus NS5A Protein Promotes Viral RNA Replication via 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, the ISG15 conjugation sites on NS5A are not well determined, and it is unclear whether the role of NS5A ISGylation in HCV replication is proviral or antiviral. Here, we investigated the role of NS5A ISGylation in HCV replication by using HCV RNA replicons that encode a mutation at each lysine (Lys) residue of the NS5A protein. Immunoblot analyses revealed that 5 Lys residues (K44, K68, K166, K215, and K308) of the 14 Lys residues within NS5A (genotype 1b, Con1) have the potential to accept ISGylation. We tested the NS5A ISGylation among different HCV genotypes and observed that the NS5A proteins of all of the HCV genotypes accept ISGylation at multiple Lys residues. Using an HCV luciferase reporter replicon assay revealed that 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 derived from all of the HCV genotypes suggesting that NS5A ISGylation enhances the interaction between NS5A and CypA. Taken together, these results suggest that NS5A ISGylation functions as a proviral factor and promotes HCV replication via the recruitment of CypA.IMPORTANCE Host 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.

  Sep. 2020, Journal of virology, 94(20) (20), English, International magazine

  [Refereed]

  Scientific journal


• 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

  Mar. 2019, Journal of virology, 93(6) (6), English, International magazine

  [Refereed]

  Scientific journal


• 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

  Group A rotavirus (RVA) is the most important cause of severe gastroenteritis among children worldwide, and effective RVA vaccines have been introduced in many countries. Here we performed a molecular epidemiological analysis of RVA infection among pediatric patients in East Java, Indonesia, during 2015-2018. A total of 432 stool samples were collected from hospitalized pediatric patients with acute gastroenteritis. None of the patients in this cohort had been immunized with an RVA vaccine. The overall prevalence of RVA infection was 31.7% (137/432), and RVA infection was significantly more prevalent in the 6- to 11-month age group than in the other age groups (P < 0.05). Multiplex reverse transcription-PCR (RT-PCR) revealed that the most common G-P combination was equine-like G3P[8] (70.8%), followed by equine-like G3P[6] (12.4%), human G1P[8] (8.8%), G3P[6] (1.5%), and G1P[6] (0.7%). Interestingly, the equine-like strains were exclusively detected until May 2017, but in July 2017 they were completely replaced by a typical human genotype (G1 and G3), suggesting that the dynamic changes in RVA genotypes from equine-like G3 to typical human G1/G3 in Indonesia can occur even in the country with low RVA vaccine coverage rate. The mechanism of the dynamic changes in RVA genotypes needs to be explored. Infants and children with RVA-associated gastroenteritis presented more frequently with some dehydration, vomiting, and watery diarrhea, indicating a greater severity of RVA infection compared to those with non-RVA gastroenteritis. In conclusion, a dynamic change was found in the RVA genotype from equine-like G3 to a typical human genotype. Since severe cases of RVA infection were prevalent, especially in children aged 6 to 11 months or more generally in those less than 2 years old, RVA vaccination should be included in Indonesia's national immunization program.

  2019, Frontiers in microbiology, 10, 940 - 940, English, International magazine, Co-authored internationally

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 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.

  Jul. 2018, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 61, 224 - 228, English, International magazine, Co-authored internationally

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Hepatitis C virus NS5A protein promotes the lysosomal degradation of hepatocyte nuclear factor 1α via chaperonemediated autophagy

  Chieko Matsui, Lin Deng, Nanae Minami, Takayuki Abe, Kazuhiko Koike, Ikuo Shoji

  American Society for Microbiology, Jul. 2018, Journal of Virology, 92(13) (13), English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 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

  Nov. 2017, INFECTION GENETICS AND EVOLUTION, 55, 1 - 7, English, International magazine, Co-authored internationally

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 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

  Jul. 2017, MICROBIOLOGY AND IMMUNOLOGY, 61(7) (7), 287 - 292, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 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, Dec. 2015, 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], Japanese


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

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

  Aug. 2015, JOURNAL OF GENERAL VIROLOGY, 96(8) (8), 2200 - 2205, English, International magazine

  [Refereed]

  Scientific journal


• 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

  Aug. 2015, MICROBIOLOGY AND IMMUNOLOGY, 59(8) (8), 466 - 476, English, International magazine, Co-authored internationally

  [Refereed]

  Scientific journal


• Hepatitis C virus-induced glucose metabolic disorder.

  Shoji I, Deng L, Matsui C, Hotta H

  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.

  日本ウィルス学会, 2015, Uirusu, 65(2) (2), 263 - 268, Japanese, Domestic magazine

  [Refereed]

  Scientific journal


• Hepatitis C Virus Infection Suppresses GLUT2 Gene Expression via Downregulation of Hepatocyte Nuclear Factor 1 alpha

  Chieko Matsui, Ikuo Shoji, Shusaku Kaneda, Imelda Rosalyn Sianipar, Lin Deng, Hak Hotta

  Dec. 2012, JOURNAL OF VIROLOGY, 86(23) (23), 12903 - 12911, English, International magazine

  [Refereed]

  Scientific journal

• HCV感染における転写因子の蛋白質分解を介した病態への影響

  松井千絵子

  2021, ひょうご科学技術協会研究成果報告書(Web), 2021


• 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, 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, 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, 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, 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, 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, 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, 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 4.C型肝炎ウイルスによる糖代謝異常

  勝二郁夫, DENG Lin, 松井千絵子, 堀田博

  2015

• Molecular mechanism of HCV proliferation via selective lysosomal protein degradation pathways

  松井千絵子, SEPTIANASTITI Maria Alethea, 徐子涵, とう琳, 阿部隆之, 勝二郁夫

  日本ウイルス学会学術集会プログラム・予稿集(Web), 2023


• Unusual G9P[4] rotavirus emerged after the dynamic changes in rotavirus genotypes from equine-like G3 to typical human G1/G3 in Indonesia

  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

  日本ウイルス学会学術集会プログラム・予稿集(Web), 2023


• HCV感染はANX5とPKC-etaによるoccludinの機能制御に干渉することでウイルス伝播を促進させる

  阿部隆之, 松井千絵子, とう琳, 松浦善治, 勝二郁夫

  日本ウイルス学会学術集会プログラム・予稿集(Web), 2022


• C型肝炎ウイルスが誘導する新規選択的蛋白質分解経路

  松井千絵子, YULIANDARI Putu, YULIANDARI Putu, SEPTIANASTITI Maria Alethea, とう琳, 阿部隆之, 勝二郁夫

  日本ウイルス学会学術集会プログラム・予稿集(Web), 2022


• Screening for anti-hepatitis B virus activity using heterocyclic compounds and HBV-NanoLuc reporter gene

  黒木大祐, 阿部隆之, 松井千絵子, とう琳, 武田紀彦, 安井基博, 上田昌史, 沖津貴志, 山野由美子, 波多野学, 下遠野邦忠, 勝二郁夫

  日本ウイルス学会学術集会プログラム・予稿集(Web), 2021


• 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

  日本分子生物学会年会プログラム・要旨集(Web), 2020


• 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

  日本分子生物学会年会プログラム・要旨集(Web), 2020


• HCVによるROS/JNKシグナル経路は,E3ユビキチンリガーゼItchを活性化し,VPS4Aのポリユビキチン化を介してHCV粒子放出を促進する

  DENG Lin, ARIFFIANTO Adi, ARIFFIANTO Adi, 松井千絵子, 阿部隆之, 村松正道, 脇田隆字, 柴田秀樹, 牧正敏, 勝二郁夫

  日本分子生物学会年会プログラム・要旨集(Web), 2020


• 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

  日本ウイルス学会学術集会プログラム・予稿集(Web), 2019


• HCVによるROS/JNKシグナル経路はE3ユビキチンリガーゼItchを活性化し,VPS4Aのポリユビキチン化を介してHCV粒子放出を促進する

  とう琳, 松井千絵子, 阿部隆之, 勝二郁夫

  日本ウイルス学会学術集会プログラム・予稿集(Web), 2019


• C型肝炎ウイルス増殖を制御するアネキシン5の機能解析

  丸谷祐樹, 阿部隆之, 松井千絵子, とう琳, 松浦善治, 勝二郁夫

  日本ウイルス学会学術集会プログラム・予稿集(Web), 2019


• 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

  日本ウイルス学会学術集会プログラム・予稿集(Web), 2019


• Characterization of deubiquitinating enzyme USP15 inhibitor candidates

  Shoji Ikuo, Matsui Chieko, Deng Lin, Abe Takayuki

  Consortium of Biological Sciences 2017, Dec. 2017, English, The Molecular Biology Society of Japan, 神戸, Domestic conference

  Poster presentation


• Novel equine-like G3 rotavirus strains among children in Surabaya, Indonesia, 2015-2016

  Rury Mega Wahyuni, Utsumi Takako, Yen Hai Doan, Zayyin Dinana, 藤井 克樹, Soegeng Soegijanto, Juniastuti, Laura Navika Yamani, Matsui Chieko, Deng Lin, Abe Takayuki, Soetjipto, Maria Inge Lusida, 片山 和彦, Shoji Ikuo

  The 65th Annual Meeting of the Japanese Society for Virology, Oct. 2017, English, Japanese Society for Virology, 大阪, Domestic conference

  Poster presentation


• Norovirus infection in an asymptomatic population in Indonesia

  Utsumi Takako, Maria Inge Lusida, Zayyin Dinana, Rury Mega Wahyuni, Laura Navika, Yamani, Juniastuti, Soetjipto, Matsui Chieko, Deng Lin, Abe Takayuki, Yen Hai Doan, 藤井 克樹, 片山 和彦, Shoji Ikuo

  The 65th Annual Meeting of the Japanese Society for Virology, Oct. 2017, English, Japanese Society for Virology, 大阪, Domestic conference

  Poster presentation


• Interferon-stimulated gene 15 (ISG15) regulates HCV RNA replication via different ISGylation sites on HCV NS5A

  Abe Takayuki, 南 奈苗, 友近 拳, Matsui Chieko, Deng Lin, 福原 崇介, 松浦 善治, Shoji Ikuo

  The 65th Annual Meeting of the Japanese Society for Virology, Oct. 2017, English, The Japanese Society for Virology, 大阪, Domestic conference

  Public symposium


• Hepatitis C virus NS3/4A protease cleaves SGP20 and promotes lipid droplet growth

  Matsui Chieko, 南 奈苗, Deng Lin, Abe Takayuki, Shoji Ikuo

  The 65th Annual Meeting of the Japanese Society for Virology, Oct. 2017, Japanese, Japanese Society for Virology, 大阪, Domestic conference

  Poster presentation


• HCV infection promotes Itch ubiquitin ligase activity via activation of JNK and modulates release of infectious viral particles.

  Deng Lin, Matsui Chieko, Abe Takayuki, Shoji Ikuo

  The 65th Annual Meeting of the Japanese Society for Virology, Oct. 2017, English, The Japanese Society for Virology, 大阪, Domestic conference

  Public symposium


• Peroxiredoxin 1, a novel HBx-interacting protein, negatively regulates HBV replication through binding to HBV RNA for HBV RNA degradation

  Deng Lin, Ming Chen, Matsui Chieko, Abe Takayuki, Hak Hotta, Shoji Ikuo

  2017 International HBV Meeting., Sep. 2017, English, Organising Committee of 2017 International Meeting on Molecular Biology of Hepatitis B Viruses, Washington DC, USA, International conference

  Oral presentation


• Interferon-stimulated gene 15 (ISG15) regulates HCV RNA replication via different ISGylation sites on HCV NS5A

  Abe Takayuki, 南 奈苗, 友近 拳, Matsui Chieko, Deng Lin, 福原 崇介, 松浦 善治, Shoji Ikuo

  The 24th International Symposium on Hepatitis C virus and Related Viruses, Sep. 2017, English, Organising Committee of the 24th International Symposium on Hepatitis C Virus and Related Viruses, Massachusetts, USA, International conference

  Poster presentation


• HCV infection promotes Itch ubiquitin ligase activity via activation of JNK and modulates release of infectious viral particles.

  Deng Lin, Matsui Chieko, Abe Takayuki, Shoji Ikuo

  The 24th International Symposium on Hepatitis C Virus and Related Viruses, Sep. 2017, English, Organising Committee of the 24th International Symposium on Hepatitis C Virus and Related Viruses, Washington DC, USA, International conference

  Poster presentation


• A novel pathway for lipid droplet formation induced by hepatitis C virus

  Matsui Chieko, Nanae Minami, Deng Lin, Abe Takayuki, Shoji Ikuo

  24th International Symposium on Hepatitis C Virus and Related Viruses, Sep. 2017, English, Organising Committee of the 24th International Symposium on Hepatitis C Virus and Related Viruses, Cape Cod, USA, International conference

  Poster presentation


• Norovirus and Rotavirus Infections among Hospitalized Children with Acute Gastroenteritis in Surabaya, East Java, Indonesia

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

  2nd Molecular, Cellular, and Life Sciences 2017, Jul. 2017, English, Osaka University and Universitas Airlangga, Surabaya, Indonesia, International conference

  Oral presentation


• Selective protein degradation via HCV-induced chaperone mediated autophagy

  Shoji Ikuo, Matsui Chieko, Deng Lin, Abe Takayuki

  第37回近畿腸管微生物研究会, Jun. 2017, Japanese, 近畿腸管微生物研究会, 大阪, Domestic conference

  Oral presentation


• 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

  日本分子生物学会年会プログラム・要旨集(Web), 2016


• 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, DENG Lin

  日本生化学会大会(Web), 2015


• 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

  日本ウイルス学会学術集会プログラム・抄録集, 2014


• 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

  日本分子生物学会年会プログラム・要旨集(Web), 2014


• 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

  日本ウイルス学会学術集会プログラム・抄録集, 2013


• 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

  日本ウイルス学会学術集会プログラム・抄録集, 2013


• 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

  日本ウイルス学会学術集会プログラム・抄録集, 2012


• 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

  日本分子生物学会年会プログラム・要旨集(Web), 2012


• HCV

  Deng lin


• C型肝炎ウイルス

• C型肝炎ウイルスが関与する新規分解機構の解明

  松井 千絵子

  日本学術振興会, 科学研究費助成事業, 若手研究, 神戸大学, 01 Apr. 2022 - 31 Mar. 2025


• The molecular mechanism of HCV-induced protein degradation via chaperone mediated autophagy

  Matsui Chieko

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists, Kobe University, 01 Apr. 2019 - 31 Mar. 2021

  Chaperone mediated autophagy (CMA) carries a substrate protein into the lysosomal lumen using HSC70 and LAMP-2A. Substrate proteins of CMA contain a CMA-targeting motif, which is selectively recognized by HSC70. CMA promotes the degradation of a specific substrate protein that enters into the lysosome through LAMP-2A. We previously reported that HCV NS5A interacts with HSC70 and recruits HSC70 to substrate protein, thereby promoting the lysosomal degradation of substrate protein via CMA. More than 130 host proteins have been identified as NS5A-interacting proteins. In this study, we examined the potential CMA-targeting motif in NS5A interacting proteins. We found novel host proteins that are degraded by lysosomes via the CMA-dependent pathway.


• 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

  日本学術振興会, 科学研究費助成事業 特別研究員奨励費, 特別研究員奨励費, 神戸大学, 25 Apr. 2014 - 31 Mar. 2016

  C型肝炎ウイルス(HCV)は高率に2型糖尿病を合併することが知られているが、詳しい発症機序はいまだ明らかではない。これまでHCV蛋白質のNS5Aが、GLUT2プロモーター領域に結合する転写因子HNF-1α蛋白質のライソソーム依存性分解を誘導させ、HNF-1α蛋白質量を著しく減少させることで、GLUT2遺伝子の転写抑制、肝細胞内への糖の取り込みが抑制、さらには高血糖が引き起こされる可能性を示した。 平成27年度は、HCV NS5AによるHNF-1α蛋白質の選択的分解機構について明らかにするために、NS5AとHNF-1α蛋白質の認識機構の同定を行った。NS5AとHNF-1αの相互作用には、NS5Aのdomain Iのaa 121-126とHNF-1α POUs domain(aa 91-181)が重要であることが示唆された。NS5Aのaa 121-126のどのアミノ酸がHNF-1αとの相互作用に重要であるかを検討するために、各アミノ酸をアラニン残基に置換した変異体を作製し、HNF-1αと相互作用を検討した。その結果、NS5A Val121Ala変異でHNF-1αとの相互作用が消失し、さらにNS5AによるHNF-1α蛋白質分解が抑制された。これによりNS5A Val121がNS5AによるHNF-1α蛋白質分解に関与していることが示唆された。 HCV感染によるHNF-1α蛋白質の選択的分解にChaperone-mediated autophagy (CMA)が関与しているかを検討した。CMAに必須である細胞質シャペロンHSC70とHNF-1αの相互作用が確認された。HCV感染細胞にAutophagy阻害剤NH4Clで処理を行ったところ、HCV感染によるHNF-1α蛋白質量の減少が回復した。このことから、HCV感染はCMA pathwayを介してHNF-1α蛋白質分解を誘導する可能性が示された。