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Functional analysis of intracellular annexins involved in the propagation of hepatitis virus

Research Project

Project/Area Number 17K08857
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Virology
Research InstitutionKobe University

Principal Investigator

ABE TAKAYUKI  神戸大学, 医学研究科, 准教授 (90403203)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsC型肝炎ウイルス / アネキシン / タイトジャンクション / 細胞間極性 / 肝炎ウイルス
Outline of Final Research Achievements

Annexins (ANXs) comprise a family of calcium- and phospholipid-binding proteins and are implicated to involve in not only a numerous of cellular processes but also life-cycle of several viral infections. Here we demonstrate a novel insight of annexin A5 (ANXA5) on the HCV life-cycles. The knockdown of ANXA5 remarkably increased the expression of both HCV proteins and HCV RNA levels in the HCV replicon cells. Using an infectious HCV clones, we confirmed the significant enhancement of HCV propagation in the ANXA5 knockdown cells, suggesting that ANXA5 acts as a negative regulator of HCV infection. Furthermore, the confocal microscopic analysis revealed that ANXA5 is required for the proper cellular localization of tight-junction (TJ) proteins such as CLDN-1 and OCLN, which are critical entry factors for HCV infection. These results provide new insights into the HCV life-cycle on the function of ANXA5 that acts via modulation of TJ proteins assembly.

Academic Significance and Societal Importance of the Research Achievements

本研究の主な成果として、肝炎ウイルスに対する新たな増殖抑制因子として、アネキシン5分子を同定したことが挙げられる。また、学術的な新たな知見として、アネキシン5分子がタイトジャンクション形成の恒常性維持にも関与していることを明らかにした。タイトジャンクション形成の恒常性維持の破綻は、癌、難聴、糖尿病などの様々な疾患の要因になることが示唆されている。アネキシン5分子の機能を詳細に解析することで、肝炎ウイルスの排除のみならず、タイトジャンクション形成の恒常性維持の破綻に起因する様々な疾患に対する分子機序、ならびに治療法開発への道が開ける可能性がある。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (14 results)

All 2019 2018 2017

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (7 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Cytosolic DNA-sensing immune response and viral infection.2019

    • Author(s)
      Takayuki Abe, Yuki Marutani, and Ikuo Shoji.
    • Journal Title

      Microbiol & Immunol

      Volume: 63 Issue: 2 Pages: 51-64

    • DOI

      10.1111/1348-0421.12669

    • NAID

      120006599148

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Negative regulation of cytosolic sensing of DNA.2019

    • Author(s)
      Takayuki Abe, and Sagi D. Shapira.
    • Journal Title

      Int Rev Cell Mol Biol

      Volume: 344 Pages: 91-115

    • DOI

      10.1016/bs.ircmb.2018.09.002

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Peroxiredoxin 1, a novel HBx-interacting protein, interacts with exsome component 5 and negatively regulates hepatitis B virus (HBV) propagation through degradation of HBV RNA.2019

    • Author(s)
      Lin Deng, Xiang Gan, Masahiko Ito, Ming Chen, Hussein H. Aly, Chieko Matsui, Takayuki Abe, Koichi Watashi,Takaji Wakita, Tetsuro Suzuki, Toru Okamoto, Yoshiharu Matsuura, Masashi Mizokami, Ikuo Shoji, and Hak Hotta.
    • Journal Title

      J. Virol

      Volume: 93 Issue: 6

    • DOI

      10.1128/jvi.02203-18

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hepatitis C virus NS5A protein promotes the lysosomal degradation of hepatocyte nuclear factor 1a via chaperone-mediated autophagy.2018

    • Author(s)
      Chieko Matsui, Lin Deng, Nanae Minami, Takayuki Abe, Kazuhiko Koike, and Ikuo Shoji.
    • Journal Title

      J. Virol

      Volume: 92 Issue: 13

    • DOI

      10.1128/jvi.00639-18

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Baculovirus as a tool for gene delivery and gene therapy.2018

    • Author(s)
      Chikako Ono, Toru Okamoto, Takayuki Abe, and Yoshiharu Matsuura.
    • Journal Title

      Viruses

      Volume: 10 Issue: 9 Pages: 510-510

    • DOI

      10.3390/v10090510

    • NAID

      120006539306

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Unconjugated interferon-stimulated gene 15 specifically interacts with the hepatitis C virus NS5A protein via domain I.2017

    • Author(s)
      Nanae Minami, Takayuki Abe, Lin Deng, Chieko Matsui, Takasuke Fukuhara, Yoshiharu Matsuura, and Ikuo Shoji.
    • Journal Title

      Microbiology and Immunology

      Volume: 61 Issue: 7 Pages: 287-292

    • DOI

      10.1111/1348-0421.12493

    • NAID

      120006604679

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Germ-cell-specific inflammasome component NLRP14 negatively regulates cytosolic nucleic acid sensing to promote fertilization.2017

    • Author(s)
      Takayuki Abe, Albert Lee, Ramaswami Sitharam, Jordan Kesner, Raul Rabadan, and Sagi D. Shapira.
    • Journal Title

      Immunity

      Volume: 46 Issue: 4 Pages: 621-634

    • DOI

      10.1016/j.immuni.2017.03.020

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Annexin 5 participates in the negative regulation of HCV propagation2019

    • Author(s)
      Yuki Marutani, Takayuki Abe, Chieko Matsui, Lin Deng, Yoshiharu Matsuura, and Ikuo Shoji
    • Organizer
      67th Annual Meeting of the Japanese Society for Virology
    • Related Report
      2019 Annual Research Report
  • [Presentation] Critical role of NS5A-ISGylation in the efficient HCV RNA replication.2018

    • Author(s)
      Abe T, Minami N, Rheza Gandi Bawono, Matsui C, Deng L, Fukuhara T, Matsuura Y, and Shoji I.
    • Organizer
      66th Annual Meeting of the Japanese Society for Virology.
    • Related Report
      2018 Research-status Report
  • [Presentation] The role of ISG15-conjugation on the Hepatitis B virus HBx protein.2018

    • Author(s)
      Rheza Gandi Bawono, Abe T, Deng L, Matsui C, Shimotohno K, and Shoji I.
    • Organizer
      66th Annual Meeting of the Japanese Society for Virology.
    • Related Report
      2018 Research-status Report
  • [Presentation] Critical role of NS5A-ISGylation in the efficient HCV RNA replication.2018

    • Author(s)
      Abe T, Minami N, Rheza Gandi Bawono, Matsui C, Deng L, Fukuhara T, Matsuura Y, and Shoji I.
    • Organizer
      25th International Symposium on Hepatitis C virus and Related Viruses
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] The role of ISG15-conjugation on the Hepatitis B virus HBx protein.2018

    • Author(s)
      Abe T, Rheza Gandi Bawono, Deng L, Matsui C, Shimotohno K, and Shoji I.
    • Organizer
      2018 International HBV Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Interferon-stimulated gene 15 (ISG15) regulates HCV RNA replication via different ISGylation sites on HCV NS5A.2017

    • Author(s)
      Takayuki Abe, Nanae Minami, Ken Tomochika, Chieko Matsui, Lin Deng, Takasuke Fukuhara, Yoshiharu Matsuura, and Ikuo Shoji.
    • Organizer
      24th International Symposium on Hepatitis C virus and related viruses.
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Interferon-stimulated gene 15 (ISG15) regulates HCV RNA replication via different ISGylation sites on HCV NS5A.2017

    • Author(s)
      Takayuki Abe, Nanae Minami, Ken Tomochika, Chieko Matsui, Lin Deng, Takasuke Fukuhara, Yoshiharu Matsuura, and Ikuo Shoji.
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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