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Identification of cis-acting element for packaging of hepatitis C virus genome

Research Project

Project/Area Number 24390111
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Virology
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

SUZUKI Tetsuro  浜松医科大学, 医学部, 教授 (00250184)

Co-Investigator(Kenkyū-buntansha) SUZUKI Ryosuke  国立感染症研究所, ウイルス第二部, 主任研究官 (50342902)
ITO Masahiko  浜松医科大学, 医学部感染症学講座, 助教 (50385423)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Fiscal Year 2014: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2013: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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 / 複製 / パッケージング
Outline of Final Research Achievements

The mechanism(s) by which the hepatitis C virus (HCV) genome becomes encapsidated remains unknown. Deep sequencing demonstrated that a majority of particle-associated HCV RNAs are genome-sized. In cell cultures producing HCV, molecular ratios of 3’ end viral RNA to 5’ end positively correlated with infectivity of fractions and that of virion-rich fraction was the highest, suggesting selective encapsidation of genome RNA. Using trans-complementation systems, the 3’ untranslated region (UTR) of the genome was identified as a cis-acting element for RNA packaging. Mutations within the stem-loops at the 3’ end of the 3’ UTR were observed to diminish packaging efficiency. A foreign gene flanked by the 3’ UTR was encapsidated by supplying both viral NS3-NS5B proteins and Core-NS2 in trans. This study provides the first direct evidence of selective packaging of the HCV genome into the viral particles potentially through 3’ UTR-Core binding.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (30 results)

All 2015 2014 2013 2012

All Journal Article (16 results) (of which Peer Reviewed: 15 results,  Open Access: 5 results,  Acknowledgement Compliant: 3 results) Presentation (8 results) (of which Invited: 1 results) Book (2 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 4 results)

  • [Journal Article] Characterization of self-assembled virus-like particles of Merkel cell polyomavirus.2015

    • Author(s)
      Li TC, Iwasaki K, Katano H, Kataoka M, Nagata N, Kobayashi K, Mizutani T, Takeda N, Wakita T, Suzuki T.
    • Journal Title

      PLOS ONE

      Volume: 10 Issue: 2 Pages: 524-531

    • DOI

      10.1371/journal.pone.0115646

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Targeting cellular squalene synthase, an enzyme essential for cholesterol biosynthesis is a potential antiviral strategy against hepatitis C virus2015

    • Author(s)
      Kyoko Saito, Yoshitaka Shirasago, Tetsuro Suzuki, Hideki Aizaki, Kentaro Hanada, Takaji Wakita, Masahiro Nishijima, Masayoshi Fukasawa
    • Journal Title

      J. Virol.

      Volume: 89 Issue: 4 Pages: 2220-2232

    • DOI

      10.1128/jvi.03385-14

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Isolation and Characterization of an Huh.7.5.1-Derived Cell Clone Highly Permissive to Hepatitis C Virus2015

    • Author(s)
      Shirasago Y, Sekizuka T, Saito K, Suzuki T, Wakita T, Hanada K, Kuroda M, Abe R, Fukasawa M.
    • Journal Title

      Japanese Journal of Infectious Diseases

      Volume: 68 Issue: 2 Pages: 81-88

    • DOI

      10.7883/yoken.JJID.2014.231

    • NAID

      130004716751

    • ISSN
      1344-6304, 1884-2836
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Alternative endocytosis pathway for productive entry of hepatitis C virus.2014

    • Author(s)
      Matsuda M, Suzuki R, Kataoka C, Watashi K, Aizaki H, Kato N, Matsuura Y, Suzuki T, Wakita T
    • Journal Title

      J Gen Virol.

      Volume: 95(Pt 12) Issue: 12 Pages: 2658-67

    • DOI

      10.1099/vir.0.068528-0

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of Hepatitis C Virus NS5A Hyperphosphorylation Mediated by Casein Kinase I-α in Infectious Virus Production.2014

    • Author(s)
      Masaki T, Matsunaga S, Takahashi H, Nakashima K, Kimura Y, Ito M, Matsuda M, Murayama A, Kato T, Hirano H, Endo Y, Lemon SM, Wakita T, Sawasaki T, Suzuki T
    • Journal Title

      J Virol

      Volume: 88(13) Issue: 13 Pages: 7541-55

    • DOI

      10.1128/jvi.03170-13

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Retinoids and rexinoids inhibit hepatitis C virus independently of retinoid receptor signaling.2014

    • Author(s)
      111. Murakami Y, Fukasawa M, Kaneko Y, Suzuki T, Wakita T, Fukazawa H.
    • Journal Title

      Microbes Infect.

      Volume: 16 Issue: 2 Pages: 114-122

    • DOI

      10.1016/j.micinf.2013.10.016

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Signal peptidase complex subunit 1 participates in the assembly of hepatitis C virus through an interaction with E2 and NS22013

    • Author(s)
      Suzuki R, Matsuda M, Watashi K, Aizaki H, Matsuura Y, Wakita T, Suzuki T
    • Journal Title

      PLoS Pathog

      Volume: 9 Issue: 8 Pages: 1-12

    • DOI

      10.1371/journal.ppat.1003589

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antiviral activity of glycyrrhizin against hepatitis C virus in vitro2013

    • Author(s)
      Matsumoto Y, Matsuura T, Aoyagi H, Matsuda M, Hmwe SS, Date T, Watanabe N, Watashi K, Suzuki R, Ichinose S, Wake K, Suzuki T, Miyamura T, Wakita T, Aizaki H
    • Journal Title

      PLoS One

      Volume: 8 Issue: 7 Pages: e68992-e68992

    • DOI

      10.1371/journal.pone.0068992

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HCV NS3 protease enhancesliver fibrosis via binding to and activating TGF-β type I receptor2013

    • Author(s)
      Sakata K, Eda S, Lee E, Hara M, Imoto M, Kojima S.
    • Journal Title

      Scientific Reports

      Volume: 3 Issue: 1 Pages: 3243-3243

    • DOI

      10.1038/srep03243

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hepatitis C virus NS3/4A protease inhibits complement activation by cleaving complement component 42013

    • Author(s)
      Mawatari S, Uto H, Ido A, Nakashima K, Suzuki T, Kanmura S, Kumagai K, Oda K, Tabu K, Tamai T, Moriuchi A, Oketani M, Shimada Y, Sudoh M, Shoji I, Tsubouchi H
    • Journal Title

      PLoS One

      Volume: 8(12) Issue: 12 Pages: e82094-e82094

    • DOI

      10.1371/journal.pone.0082094

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adenovirus vectors lacking virus-associated RNA expression enhance shRNA activity to suppress hepatitis C virus replication.2013

    • Author(s)
      110. Pei Z, Shi G, Kondo S, Ito M, Maekawa A, Suzuki M, Saito I, Suzuki T, Kanegae Y.
    • Journal Title

      Scientific Reports

      Volume: 3 Issue: 1 Pages: 3575-3575

    • DOI

      10.1038/srep03575

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Replication of Hepatitis C Virus Genotype 3a in Cultured Cells.2013

    • Author(s)
      Saeed Mohsan
    • Journal Title

      Gastroenterology

      Volume: 144 Issue: 1 Pages: 56-58

    • DOI

      10.1053/j.gastro.2012.09.017

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Selective estrogen receptor modulators inhibit hepatitis C virus infection at multiple steps of the virus life cycle2013

    • Author(s)
      村上 裕子
    • Journal Title

      Microbes Infect.

      Volume: 15 Issue: 1 Pages: 45-55

    • DOI

      10.1016/j.micinf.2012.10.003

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Trans-complemented hepatitis C virus particles as a versatile tool for study of virus assembly and infection.2012

    • Author(s)
      Suzuki, R.
    • Journal Title

      Virology

      Volume: 432(1) Issue: 1 Pages: 29-38

    • DOI

      10.1016/j.virol.2012.05.033

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A celi-based microplate colorimetric screen identifies 7,8-benzoflavone and green tea gallate catechins as inhibitors of the hepatitis C virus2012

    • Author(s)
      深澤 秀輔, 他
    • Journal Title

      Biol Pharm Bull.

      Volume: 35 Pages: 1320-1327

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Morphogenesis of infectious hepatitis C virus particles2012

    • Author(s)
      鈴木 哲朗
    • Journal Title

      Frontiers in Microbiology

      Volume: 3 Pages: 38-38

    • DOI

      10.3389/fmicb.2012.00038

    • Related Report
      2012 Annual Research Report
  • [Presentation] 3’UTR of HCV genome functioned as a cis-acting packaging signal2014

    • Author(s)
      Guoli Shi, Tomomi Ando, Ryosuke Suzuki, Mami Matsuda, Masahiko Ito, Kenji Nakashima, Takaji Wakita and Tetsuro Suzuki
    • Organizer
      第62回日本ウイルス学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] HuH-7由来オーバル細胞様細胞株HdoによるHCV生活環の調節に関わる分化関連宿主因子の同定2014

    • Author(s)
      伊藤 昌彦、福原崇介、鈴木亮介、田川陽一、松浦善治、脇田隆字、鈴木哲朗
    • Organizer
      第62回日本ウイルス学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] HCV 3’ UTR as a cis-acting element required for the viral RNA encapsidation2014

    • Author(s)
      Guoli Shi, Tomomi Ando, Ryosuke Suzuki, Masahiko Ito, Kenji Nakashima, Takaji Wakita and Tetsuro Suzuki
    • Organizer
      21st International Symposium on HCV and Related Viruses
    • Place of Presentation
      Banff, Canada
    • Year and Date
      2014-09-07 – 2014-09-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Use of HuH7-derived, Bidirectional Oval-like Cells to Identify Differentiation-dependent Host Factors That are Involved in Regulation of HCV Lifecycle2014

    • Author(s)
      Masahiko Ito, Takasuke Fukuhara, Ryosuke Suzuki, Yoshiharu Matsuura, Takaji Wakita, Tetsuro Suzuki
    • Organizer
      21st International Symposium on HCV and Related Viruses
    • Place of Presentation
      Banff, Canada
    • Year and Date
      2014-09-07 – 2014-09-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] C型肝炎ウイルス粒子形成のメカニズム2013

    • Author(s)
      鈴木哲朗
    • Organizer
      日本ウイルス学会学術集会
    • Place of Presentation
      神戸市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Loss of susceptibility to HCV infection and decreased tumorigenicity mediated by reprogramming of human hepatoma cells2013

    • Author(s)
      伊藤昌彦、鈴木哲朗 他
    • Organizer
      International Symposium on hepatitis C virus and related viruses
    • Place of Presentation
      メルボルン
    • Related Report
      2013 Annual Research Report
  • [Presentation] Possible mechanism for selective packaging of HCV genome into the infectious particles2013

    • Author(s)
      史国利、鈴木哲朗 他
    • Organizer
      International Symposium on hepatitis C virus and related viruses
    • Place of Presentation
      メルボルン
    • Related Report
      2013 Annual Research Report
  • [Presentation] Permissivity of HuH-7-derived oval-like cells to HCV infection and replication2012

    • Author(s)
      伊藤 昌彦, 他
    • Organizer
      International Symposium on hepatitis C virus and related viruses
    • Place of Presentation
      ベニス(イタリア)
    • Year and Date
      2012-10-07
    • Related Report
      2012 Annual Research Report
  • [Book] 感染 炎症 免疫2014

    • Author(s)
      中島謙治、鈴木哲朗
    • Publisher
      医薬の門社
    • Related Report
      2014 Annual Research Report
  • [Book] C型肝炎ウイルスのゲノム複製や粒子形成を制御するしくみ2013

    • Author(s)
      鈴木哲朗
    • Publisher
      医薬ジャーナル
    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] アミノ基含有親水性樹脂化合物、ウイルス除去用高分子基材、ウイルス除去装置、及びウイルス除去装置の作動方法2013

    • Inventor(s)
      鈴木哲朗 他
    • Industrial Property Rights Holder
      浜松医科大学 他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-07-19
    • Related Report
      2013 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 糖鎖固定化親水性樹脂化合物、ウイルス除去用高分子基材、及び生体適合性材料2013

    • Inventor(s)
      鈴木哲朗 他
    • Industrial Property Rights Holder
      浜松医科大学 他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-07-19
    • Related Report
      2013 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 糖鎖固定化ウイルス除去用基材、及びウイルスの除去用具2012

    • Inventor(s)
      鈴木 哲朗, 他
    • Industrial Property Rights Holder
      DIC 浜松医大
    • Filing Date
      2012-08-08
    • Related Report
      2012 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 多孔性中空糸、及びウイルスの除去器具2012

    • Inventor(s)
      鈴木 哲朗, 他
    • Industrial Property Rights Holder
      DIC 浜松医大
    • Filing Date
      2012-08-08
    • Related Report
      2012 Annual Research Report
    • Overseas

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Published: 2012-04-24   Modified: 2019-07-29  

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