Mechanisms for the selective packaging of hepatitis C virus genome

• Project/Area Number: 15H04735
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Suzuki Tetsuro 浜松医科大学, 医学部, 教授 (00250184)
• Co-Investigator(Kenkyū-buntansha): 鈴木 亮介 国立感染症研究所, ウイルス第二部, 主任研究官 (50342902) ; 伊藤 昌彦 浜松医科大学, 医学部, 助教 (50385423)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000); Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2016: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2015: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: ウイルス / ゲノムパッケージング / 粒子形成 / C型肝炎ウイルス / パッケージング / 細胞・複製 / 微生物 / 感染症

Outline of Final Research Achievements

Our former study demonstrated that the 3’ untranslated region (UTR) of HCV genome functions as a cis-acting element for the viral RNA packaging; however, the detailed functional mechanisms of packaging signal still remain unclear. In this study, mutations within the conserved stem-loops of the 3’ UTR were observed to diminish packaging efficiency, suggesting the conserved apical loop motifs of the 3´ end-side of 3’ UTR are important for the packaging, A foreign reporter gene flanked by the 3’ UTR was encapsidated by supplying both viral NS3-NS5B proteins and Core-NS2 in trans. The 3’ UTRs derived from GT-2a and -1a supported the packaging at comparable level. It is highly likely that specific recognition of the HCV genome via the packaging signal and coupling with replication are not mutually exclusive, but rather cooperate for the best beneficial of encapsidation and nuclecapsid formation.

Research Products

• [Journal Article] Critical role of CREBH-mediated induction of transforming growth factor β2 by hepatitis C virus infection in fibrogenic responses in hepatic stellate cells (2017)
  • Author(s): Chida Takeshi、Ito Masahiko、Nakashima Kenji、Kanegae Yumi、Aoshima Takuya、Takabayashi Shuji、Kawata Kazuhito、Nakagawa Yoshimi、Yamamoto Masahiro、Shimano Hitoshi、Matsuura Tomokazu、Kobayashi Yoshimasa、Suda Takafumi、Suzuki Tetsuro
  • Journal Title: Hepatology Volume: 66 Issue: 5 Pages: 1430-1443
  • DOI: 10.1002/hep.29319
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Development of hepatoma-derived, bidirectional oval-like cells as a model to study host interactions with hepatitis C virus during differentiation (2017)
  • Author(s): Ito Masahiko、Sun Suofeng、Fukuhara Takasuke、Suzuki Ryosuke、Tamai Miho、Yamauchi Toyohiko、Nakashima Kenji、Tagawa Yoh-ichi、Okazaki Shigetoshi、Matsuura Yoshiharu、Wakita Takaji、Suzuki Tetsuro
  • Journal Title: Oncotarget Volume: 8 Issue: 33 Pages: 53899-53915
  • DOI: 10.18632/oncotarget.19108
  • Peer Reviewed / Open Access
• [Journal Article] Nonstructural 5A Protein of Hepatitis C Virus Interferes with Toll-Like Receptor Signaling and Suppresses the Interferon Response in Mouse Liver. (2017)
  • Author(s): Tsutsumi T, Okushin K, Enooku K, Fujinaga H, Moriya K, Yotsuyanagi H, Aizaki H, Suzuki T, Matsuura Y, Koike K.
  • Journal Title: PLOS One Volume: 12 Issue: 1 Pages: 2017-2017
  • DOI: 10.1371/journal.pone.0170461
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Localized surface plasmon resonance-mediated fluorescence signals in plasmonic nanoparticle-quantum dot hybrids for ultrasensitive Zika virus RNA detection via hairpin hybridization assays. (2017)
  • Author(s): Adegoke O, Morita M, Kato T, Ito M, Suzuki T, Park EY.
  • Journal Title: Biosens Bioelectron. Volume: 94 Pages: 513-522
  • DOI: 10.1016/j.bios.2017.03.046
  • NAID: 120006542499
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Occludin-Knockout Human Hepatic Huh7.5.1-8-Derived Cells Are Completely Resistant to Hepatitis C Virus Infection (2016)
  • Author(s): Yoshitaka Shirasago, Yoshimi Shimizu, Isei Tanida, Tetsuro Suzuki, Ryosuke Suzuki, Kazuo Sugiyama, Takaji Wakita, Kentaro Hanada, Kiyohito Yagi, Masuo Kondoh, and Masayoshi Fukasawa
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 39 Issue: 5 Pages: 839-848
  • DOI: 10.1248/bpb.b15-01023
  • NAID: 130005149248
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] LUC7L3/CROP inhibits replication of hepatitis B virus via suppressing enhancer II/basal core promoter activity. (2016)
  • Author(s): Li Y, Ito M, Sun S, Chida T, Nakashima K, Suzuki T.
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 36741-36741
  • DOI: 10.1038/srep36741
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Prolactin Regulatory Element Binding Protein Is Involved in Hepatitis C Virus Replication by Interaction with NS4B (2016)
  • Author(s): Kong L, Fujimoto A, Nakamura M, Aoyagi H, Matsuda M, Watashi K, Suzuki R, Arita M, Yamagoe S, Dohmae N, Suzuki T, Sakamaki Y, Ichinose S, Suzuki T, Wakita T, Aizaki H
  • Journal Title: J Virol Volume: 90 Issue: 6 Pages: 3093-3111
  • DOI: 10.1128/jvi.01540-15
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Single-domain Intrabodies against HCV Core Inhibit Viral Propagation and Core-induced NF-κB Activation (2016)
  • Author(s): Suzuki R, Saito K, Matsuda M, Sato M, Kanegae Y, Shi G, Watashi K, Aizaki H, Chiba J, Saito I, Wakita T, Suzuki T
  • Journal Title: J Gen Virol Volume: 印刷中 Issue: 4 Pages: 887-892
  • DOI: 10.1099/jgv.0.000423
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Involvement of the 3' Untranslated Region in Encapsidation of the Hepatitis C Virus (2016)
  • Author(s): Shi G, Ando T, Suzuki R, Matsuda M, Nakashima K, Ito M, Omatsu T, Oba M, Ochiai H, Kato T, Mizutani T, Sawasaki T, Wakita T, Suzuki T.
  • Journal Title: PLoS Pathog Volume: 12(2) Issue: 2 Pages: e1005441-e1005441
  • DOI: 10.1371/journal.ppat.1005441
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Monoclonal antibodies against extracellular domains of claudin-1 block hepatitis C virus infection in a mouse model (2015)
  • Author(s): Masayoshi Fukasawa, Shotaro Nagase, Yoshitaka Shirasago, Manami Iida, Mayo Yamashita, Kohki Endo, Kiyohito Yagi, Tetsuro Suzuki, Takaji Wakita, Kentaro Hanada, Hiroki Kuniyasu, Masuo Kondoh
  • Journal Title: J Virol Volume: 89 Issue: 9 Pages: 4866-4879
  • DOI: 10.1128/jvi.03676-14
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Seroprevalence of trichodysplasia spinulosa-associated polyomavirus in Japan. (2015)
  • Author(s): 122.Fukumoto H, Li TC, Kataoka M, Hasegawa H, Wakita T, Saeki H, Suzuki T, Katano H.
  • Journal Title: J. Clin. Virol. Volume: 65 Pages: 76-82
  • DOI: 10.1016/j.jcv.2015.02.014
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Pim Kinase Interacts with Nonstructural 5A Protein and Regulates Hepatitis C Virus Entry. (2015)
  • Author(s): 123.Park C, Min S, Park EM, Lim YS, Kang S, Suzuki T, Shin EC, Hwang SB.
  • Journal Title: J. Virol. Volume: 89 Issue: 19 Pages: 10073-10086
  • DOI: 10.1128/jvi.01707-15
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Hepatitis B virus efficiently infects non-adherent hepatoma cells via human sodium taurocholate cotransporting polypeptide. (2015)
  • Author(s): Okuyama-Dobashi K, Kasai H, Tanaka T, Yamashita A, Yasumoto J, Chen W, Okamoto T, Maekawa S, Watashi K, Wakita T, Ryo A, Suzuki T, Matsuura Y, Enomoto N, Moriishi K.
  • Journal Title: Scientific reports Volume: 5 Issue: 1 Pages: 17047-17047
  • DOI: 10.1038/srep17047
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 1.Critical role of CREBH-dependent transcriptional activation of TGF-beta2 by HCV infection in profibrogenic responses in hepatic stellate cells. (2017)
  • Author(s): Ito M, Chida T, Nakashima K, Kawata K, Kobayashi Y, Suda T, Suzuki T.
  • Organizer: 第65回日本ウイルス学会学術集会
• [Presentation] 2.CREBH-dependent up-regulation of profibrogenic response induced by HCV in a mouse model as well as in co-cultured cells. (2017)
  • Author(s): Chida T, Ito M, Nakashima K, Suzuki T.
  • Organizer: 24th International Symposium on Hepatitis C Virus and Related Viruses.
  • Int'l Joint Research
• [Book] Hepatitis C Virus Replication. in "Organelle Contact Sites, From Molecular Mechanism to Disease. Advances in Experimental Medicine and Biology." (2017)
  • Author(s): Suzuki T
  • Total Pages: 257
  • Publisher: Springer, Singapore
  • ISBN: 9789811045660
• [Book] Hepatitis C Virus I Cellular and Molecular Virology (2016)
  • Author(s): Suzuki T, Suzuki R.
  • Total Pages: 20
  • Publisher: Springer