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Study on molecular mechanism of herpesvirus tropism

Research Project

Project/Area Number 20H03496
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49060:Virology-related
Research InstitutionKobe University

Principal Investigator

Arii Jun  神戸大学, 医学研究科, 特命准教授 (30704928)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2021: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2020: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Keywordsヘルペスウイルス / MEK/ERK / 脂質 / ウイルス増殖 / NF-kB / ATF1 / IFN / 転写因子 / ウイルス / 細胞指向性 / 指向性 / 病態発現機構 / 特異性 / T細胞
Outline of Research at the Start

ヒトを宿主とする9種のヘルペスウイルスは、それぞれが多彩な病態を引き起こす。これらは、類似した遺伝子群を持ち、ゲノム複製、粒子形成機構はほぼ同一である。このようなウイルスが、生体内においてどのように棲み分け、異なる病態を引き起こすのか、本質的には解明されていない。本研究は、上皮への指向性の強い単純ヘルペスウイルス(HSV)および、T細胞のみで増殖するヒトヘルペスウイルス6(HHV-6)という対照的なウイルスが、どのようにこれらの細胞を好むのか、その分子機構を解明することを目指す。本研究により、医学上重要なヘルペスウイルスの病態発現機構の理解と、その治療法開発が促進されると考えられる。

Outline of Final Research Achievements

The nine species of human herpesviruses cause their own characteristic pathologies, but it is not known how their tropism is determined. This study aimed to elucidate the molecular mechanisms by which herpesviruses prefer their respective target cells. The study revealed the molecular basis for the efficient cell-to-cell transmission of HSV-1, which prefers epithelia, and the contribution of glycerophospholipids in viral replication. Furthermore, we showed a specific interaction between HHV-6A, which has a relatively slow infection cycle and prefers T cells, and cell signaling. This study may reveal some of the virus-host interactions required for the adaptation of diverse herpesviruses to their respective target cells.

Academic Significance and Societal Importance of the Research Achievements

ヒトを宿主とするヘルペスウイルスは9種存在するが、その中には抗ウイルス剤がほぼ効果がないものも存在する。本研究では、これらのヘルペスウイルスがそれぞれの標的細胞での増殖に必要な宿主因子を複数取得した。特にグリセロリン脂質であるPEの産生に関わるPcyt2の阻害剤は、マウス病態モデルにおける脳炎発症を抑制可能であった。すなわち、本研究は、さまざまなヘルペスウイルスに効果のある治療・予防薬を創生するための基盤となりうると考えられる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (20 results)

All 2022 2021 2020 Other

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Book (2 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Human Herpesvirus 6A Replication via Beta Interferon Induction.2022

    • Author(s)
      1.Aktar S, Arii J, Nguyen TTH, Huang JR, Nishimura M, Mori Y.
    • Journal Title

      J Virol.

      Volume: 96 Issue: 19

    • DOI

      10.1128/jvi.01264-22

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of the orphan transporter SLC35E1 in the nuclear egress of herpes simplex virus 12022

    • Author(s)
      Fumio Maeda, Akihisa Kato, Kosuke Takeshima, Misato Shibazaki, Ryota Sato, Takuma Shibata, Kensuke Miyake, Hiroko Kozuka-Hata, Masaaki Oyama, Eigo Shimizu, Seiya Imoto, Satoru Miyano, Shungo Adachi, Tohru Natsume, Koh Takeuchi, Yuhei Maruzuru, Naoto Koyanagi, Jun Arii, Yasushi Kawaguchi
    • Journal Title

      Journal of Virology

      Volume: - Issue: 10 Pages: 10-10

    • DOI

      10.1128/jvi.00306-22

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of the Arginine Cluster in the Disordered Domain of Herpes Simplex Virus 1 UL34 for the Recruitment of ESCRT-III for Viral Primary Envelopment2022

    • Author(s)
      Arii Jun、Takeshima Kosuke、Maruzuru Yuhei、Koyanagi Naoto、Nakayama Yoshitaka、Kato Akihisa、Mori Yasuko、Kawaguchi Yasushi
    • Journal Title

      Journal of Virology

      Volume: 96 Issue: 2

    • DOI

      10.1128/jvi.01704-21

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 2.Aktar S, Arii J*, Tjan LH, Nishimura M, Mori Y. Human Herpesvirus 6A Tegument Protein U14 Induces NF-κB Signaling by Interacting with p65.2021

    • Author(s)
      Aktar S, Arii J*, Tjan LH, Nishimura M, Mori Y.
    • Journal Title

      J Virol.

      Volume: 95 Issue: 23

    • DOI

      10.1128/jvi.01269-21

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of Phosphatidylethanolamine Biosynthesis in Herpes Simplex Virus 1-Infected Cells in Progeny Virus Morphogenesis in the Cytoplasm and in Viral Pathogenicity in Vivo2020

    • Author(s)
      Arii Jun、Fukui Ayano、Shimanaka Yuta、Kono Nozomu、Arai Hiroyuki、Maruzuru Yuhei、Koyanagi Naoto、Kato Akihisa、Mori Yasuko、Kawaguchi Yasushi
    • Journal Title

      Journal of Virology

      Volume: 94 Issue: 24

    • DOI

      10.1128/jvi.01572-20

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ESCRT-III controls nuclear envelope deformation induced by progerin2020

    • Author(s)
      Arii Jun、Maeda Fumio、Maruzuru Yuhei、Koyanagi Naoto、Kato Akihisa、Mori Yasuko、Kawaguchi Yasushi
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 18877-18877

    • DOI

      10.1038/s41598-020-75852-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prohibitin-1 Contributes to Cell-to-Cell Transmission of Herpes Simplex Virus 1 via the MAPK/ERK Signaling Pathway2020

    • Author(s)
      Watanabe Mizuki、Arii Jun、Takeshima Kosuke、Fukui Ayano、Shimojima Masayuki、Kozuka-Hata Hiroko、Oyama Masaaki、Minamitani Takeharu、Yasui Teruhito、Kubota Yuji、Takekawa Mutsuhiro、Kosugi Isao、Maruzuru Yuhei、Koyanagi Naoto、Kato Akihisa、Mori Yasuko、Kawaguchi Yasushi
    • Journal Title

      Journal of Virology

      Volume: 95 Issue: 3

    • DOI

      10.1128/jvi.01413-20

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ATF1 restricts human herpesvirus 6A replication via IFN-beta induction2022

    • Author(s)
      S Aktar, J Arii, N Huong, J Huang, M Nishimura and Y Mori,
    • Organizer
      46th ANNUAL INTERNATIONAL HERPESVIRUS WORKSHOP
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ATF1はIFN応答を介してHHV-6Aの増殖を抑制する2022

    • Author(s)
      有井 潤、S Aktar、T Nguyen、J Huang、西村光広、森 康子
    • Organizer
      第69回日本ウイルス学会学術集会
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
  • [Presentation] 転写因子ATF1 はHHV-6A の増殖を抑制する2022

    • Author(s)
      有井 潤、S Aktar、T Nguyen、J Huang、 西村光広、森 康子
    • Organizer
      第35回ヘルペスウイルス研究会
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
  • [Presentation] ヘルペスウイルス治療薬開発を目指したウイルス粒子形成機構の解析2022

    • Author(s)
      有井 潤
    • Organizer
      第63回日本臨床ウイルス学会
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Invited
  • [Presentation] Human herpesvirus 6A tegument protein U14 induces NF-κB signaling by interacting with p652021

    • Author(s)
      1.Salma Aktar, ○Jun Arii (Presenter), Lidya Handayani Tjan, Mitsuhiro Nishimura, and Yasuko Mori,
    • Organizer
      The 19th Awaji international forum on infection and immunity
    • Related Report
      2021 Annual Research Report
  • [Presentation] Human herpesvirus 6A tegument protein U14 induces NF-κB signaling by interacting with p652021

    • Author(s)
      Salma Aktar, Jun Arii, Lidiya Handayani Tjan, Mitsuhiro Nishimura, Yasuko Mori
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] HHV-6Bのウイルス学2021

    • Author(s)
      有井 潤
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Book] 臨床とウイルス ヘルペスウイルス治療薬開発を目指したウイルス粒子形成機構の解析2022

    • Author(s)
      有井 潤
    • Total Pages
      5
    • Publisher
      春恒社
    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
  • [Book] 日本医師会雑誌2020

    • Author(s)
      森 康子、有井 潤
    • Publisher
      日本医師会
    • Related Report
      2020 Annual Research Report
  • [Remarks] 研究室のホームページ

    • URL

      https://www.med.kobe-u.ac.jp/virol/index.html

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
  • [Remarks] research map

    • URL

      https://researchmap.jp/junarii

    • Related Report
      2020 Annual Research Report
  • [Remarks] homepage

    • URL

      https://www.med.kobe-u.ac.jp/virol/index.html

    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] 新規ウイルス増殖阻害剤2020

    • Inventor(s)
      川口 寧、有井 潤
    • Industrial Property Rights Holder
      国立大学法人東京大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-158247
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

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