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Infection with flaviviruses requires BCLXL for cell survival

Research Project

Project/Area Number 16K19139
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Virology
Research InstitutionOsaka University

Principal Investigator

TORU OKAMOTO  大阪大学, 微生物病研究所, 准教授 (80628595)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsフラビウイルス / アポトーシス / BCL2 / 貪食 / 細胞死 / ウイルス学
Outline of Final Research Achievements

In this study, we examined the roles of BCL2 proteins in the induction of apoptosis in cells upon infection with flaviviruses, such as Japanese encephalitis virus, Dengue virus and Zika virus. We showed that survival of the infected cells depends on BCLXL, a pro-survival BCL2 protein due to suppression of the expression of another pro-survival protein, MCL1. Treatment with BCLXL inhibitors, as well as deficient BCLXL gene expression, induced BAX/BAK-dependent apoptosis upon infection with flaviviruses. Furthermore, we examined the roles of BCLXL in the death of JEV-infected cells during in vivo infection. Haploinsufficiency of the BCLXL gene, as well as administration of BH3 mimetic compounds, produced resistance to the lethal challenge of JEV infection and suppressed inflammation. These results suggest that BCLXL plays a crucial role in the survival of cells infected with flaviviruses.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (5 results)

All 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Regulation of Apoptosis during Flavivirus Infection.2017

    • Author(s)
      Okamoto T, Suzuki T, Kusakabe S, Tokunaga M, Hirano J, Miyata Y, Matsuura Y
    • Journal Title

      Viruses

      Volume: 9 Issue: 9 Pages: 243-243

    • DOI

      10.3390/v9090243

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] フラビウイルス感染におけるBcl-2ファミリー蛋白質の制御2017

    • Author(s)
      岡本徹
    • Organizer
      東京大学医科学研究所、若手研究者シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] BCLXL dependent survivals upon infection with Flaviviruses2017

    • Author(s)
      鈴木達也
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] BCLXL dependent survivals upon infection with Flaviviruses2017

    • Author(s)
      鈴木達也
    • Organizer
      The American Society for Virology (ASV) the 36th Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] BCLXL dependent survivals upon infection with Flaviviruses2017

    • Author(s)
      鈴木達也
    • Organizer
      第16回あわじしま感染症・免疫フォーラム
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2019-03-29  

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