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HIV-1感染における内因性免疫と獲得免疫の相反原理の解明

Research Project

Project/Area Number 19J20488
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Review Section Basic Section 49060:Virology-related
Research InstitutionThe University of Tokyo

Principal Investigator

木村 出海  東京大学, 新領域創成科学研究科, 特別研究員(DC1)

Project Period (FY) 2019-04-25 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2021: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2020: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2019: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsHIV / 内因性免疫 / 獲得免疫 / APOBEC3
Outline of Research at the Start

抗レトロウイルス薬多剤併用療法の確立・発展により、AIDSの発症を抑制することが可能になっている。しかし、HIV-1感染に対する根治療法はいまだに確立されていない。この主因として、HIV-1感染者が示す病態進行・予後には個人差があり、この差異を規定する分子メカニズムがほとんど明らかになっていない、ということが挙げられる。この問題に対し、ヒト白血球型抗原 (HLA)の多型が、感染者ごとの病態の差異を生みだす因子として明らかになっている。そこで本研究では、HLA多型のひとつであるHLA-B35に着目し、この多型がHIV-1感染症において病態進行のリスクファクターとなる分子メカニズムを解析する。

Outline of Annual Research Achievements

本研究の目的は、「HLA-B35拘束性のCTL応答から逃避することで生じたE76K変異体は、APOBEC3Fによってもたらされる変異によって多様化し、病態進行を亢進する。これが、HLA-B35がHIV-1感染に対するリスクファクターとなる原因のひとつである」という仮説を検証することである。本検証により、HIV-1感染者それぞれが示す病態進行と予後になぜ個人差が生じるのか、その分子メカニズムの一端の解明へとつながることが期待される。この目的を達成するために、昨年度は、初年度に構築したIn vitro実験系に必要な材料を用いて、実際に変異ウイルスを取得するためのIn vitro感染実験を行なった。具体的には、ウイルスの感染が完全に阻害されることなく、細胞の増殖速度とウイルス感染による細胞死の速度が平衡状態を保つような一定の薬剤濃度でウイルス感染細胞を長期間培養する手法、培養期間とともに徐々に薬剤の濃度を上げていく手法、ウイルスプラスミドとAPOBEC3F発現ベクターを細胞に一過性にco-transfectionし、上清中に放出されたAPOBEC3F結合ウイルスを回収、そのウイルスを新しい細胞にsingle round infectionさせ、放出されたウイルスを回収することで、APOBEC3Fによる過剰な変異挿入を防ぐ実験系といった複数の実験系を用いて変異ウイルスの取得を試みた。しかし、変異ウイルスの取得には至らなかった。

Research Progress Status

令和3年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和3年度が最終年度であるため、記入しない。

Report

(3 results)
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (19 results)

All 2022 2021 2020

All Journal Article (13 results) (of which Int'l Joint Research: 13 results,  Peer Reviewed: 12 results,  Open Access: 13 results) Presentation (6 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] The SARS-CoV-2 Lambda variant exhibits enhanced infectivity and immune resistance2022

    • Author(s)
      Kimura Izumi、Kosugi Yusuke、Wu Jiaqi、other 17 authors、Saito Akatsuki、Nakagawa So、Sato Kei
    • Journal Title

      Cell Reports

      Volume: 38 Issue: 2 Pages: 110218-110218

    • DOI

      10.1016/j.celrep.2021.110218

    • NAID

      120007183813

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity2022

    • Author(s)
      Meng Bo、Abdullahi Adam、Ferreira Isabella A. T. M.、Goonawardane Niluka、Saito Akatsuki、Kimura Izumi、Yamasoba Daichi、Other 48 authors、Sato Kei、Gupta Ravindra K.
    • Journal Title

      Nature

      Volume: 603 Issue: 7902 Pages: 706-714

    • DOI

      10.1038/s41586-022-04474-x

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Attenuated fusogenicity and pathogenicity of SARS-CoV-2 Omicron variant2022

    • Author(s)
      Suzuki Rigel、Yamasoba Daichi、Kimura Izumi、Wang Lei他
    • Journal Title

      Nature

      Volume: 603 Issue: 7902 Pages: 700-705

    • DOI

      10.1038/s41586-022-04462-1

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity2021

    • Author(s)
      Motozono Chihiro、Toyoda Mako、Zahradnik Jiri、Saito Akatsuki、Other 19 authors、Ikeda Terumasa、Nakagawa So、Ueno Takamasa、Sato Kei
    • Journal Title

      Cell Host & Microbe

      Volume: 29 Issue: 7 Pages: 1124-1136

    • DOI

      10.1016/j.chom.2021.06.006

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SARS-CoV-2 B.1.617 Mutations L452R and E484Q Are Not Synergistic for Antibody Evasion2021

    • Author(s)
      Ferreira IATM, Kemp SA, Datir R, Saito A, Meng B, Rakshit P, Takaori-Kondo A, Kosugi Y, Uriu K, Kimura I, Shirakawa K, Abdullahi A, Agarwal A, Ozono S, Tokunaga K, Sato K, Gupta RK
    • Journal Title

      The Journal of Infectious Diseases

      Volume: 224 Issue: 6 Pages: 989-994

    • DOI

      10.1093/infdis/jiab368

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neutralization of the SARS-CoV-2 Mu Variant by Convalescent and Vaccine Serum2021

    • Author(s)
      Uriu Keiya、Kimura Izumi、Shirakawa Kotaro、Takaori-Kondo Akifumi、Nakada Taka-aki、Kaneda Atsushi、Nakagawa So、Sato Kei
    • Journal Title

      New England Journal of Medicine

      Volume: 385 Issue: 25 Pages: 2397-2399

    • DOI

      10.1056/nejmc2114706

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation2021

    • Author(s)
      Saito Akatsuki、Irie Takashi、Suzuki Rigel、Maemura Tadashi、Nasser Hesham、Uriu Keiya、Kosugi Yusuke、Other 43 authors、Tanaka Shinya、Nakagawa So、Ikeda Terumasa、Fukuhara Takasuke、Kawaoka Yoshihiro、Sato Kei、The Genotype to Phenotype Japan (G2P-Japan) Consortium
    • Journal Title

      Nature

      Volume: 602 Issue: 7896 Pages: 300-306

    • DOI

      10.1038/s41586-021-04266-9

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sarbecovirus ORF6 proteins hamper the induction of interferon signaling2021

    • Author(s)
      Kimura I, Konno Y, Uriu K, Hopfensperge K, Sauter D, Nakagawa S, Sato K
    • Journal Title

      Cell Reports

      Volume: 34 Issue: 13 Pages: 108916-108916

    • DOI

      10.1016/j.celrep.2021.108916

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A comprehensive investigation on the interplay between feline APOBEC3Z3 proteins and feline immunodeficiency virus Vif proteins. Journal of Virology.2021

    • Author(s)
      Yusuke Kosugi‡, Keiya Uriu‡, Narumi Suzuki‡, Keisuke Yamamoto‡, Shumpei Nagaoka‡, Izumi Kimura‡, Yoriyuki Konno‡, Hirofumi Aso‡, Brian J Willett, Tomoko Kobayashi, Yoshio Koyanagi, Mahoko Takahashi Ueda, Jumpei Ito and Kei Sato. ‡Equal contribution.
    • Journal Title

      Journal of Virology

      Volume: 00178-21 Issue: 13 Pages: 00-00

    • DOI

      10.1128/jvi.00178-21

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans2020

    • Author(s)
      Nakano Yusuke、Yamamoto Keisuke、Ueda Mahoko Takahashi、Soper Andrew、Konno Yoriyuki、Kimura Izumi、Uriu Keiya、Kumata Ryuichi、Aso Hirofumi、Misawa Naoko、Nagaoka Shumpei、Shimizu Soma、Mitsumune Keito、Kosugi Yusuke、Juarez-Fernandez Guillermo、Ito Jumpei、...、Koyanagi Yoshio、Harris Reuben S.、Sato Kei
    • Journal Title

      PLOS Pathogens

      Volume: 16 Issue: 9 Pages: 1008812-1008812

    • DOI

      10.1371/journal.ppat.1008812

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SARS-CoV-2 ORF3b Is a Potent Interferon Antagonist Whose Activity Is Increased by a Naturally Occurring Elongation Variant2020

    • Author(s)
      Konno Yoriyuki、Kimura Izumi、Uriu Keiya、Fukushi Masaya、Irie Takashi、Koyanagi Yoshio、Sauter Daniel、Gifford Robert J.、Nakagawa So、Sato Kei
    • Journal Title

      Cell Reports

      Volume: 32 Issue: 12 Pages: 108185-108185

    • DOI

      10.1016/j.celrep.2020.108185

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Endogenous retroviruses drive KRAB zinc-finger protein family expression for tumor suppression2020

    • Author(s)
      Ito Jumpei、Kimura Izumi、Soper Andrew、Coudray Alexandre、Koyanagi Yoshio、Nakaoka Hirofumi、Inoue Ituro、Turelli Priscilla、Trono Didier、Sato Kei
    • Journal Title

      Science Advances

      Volume: 6 Issue: 43 Pages: 3020-3020

    • DOI

      10.1126/sciadv.abc3020

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Endogenous retroviruses drive KRAB zinc-finger family protein expression for tumor suppression2020

    • Author(s)
      Ito Jumpei、Kimura Izumi、Soper Andrew、Coudray Alexandre、Koyanagi Yoshio、Nakaoka Hirofumi、Inoue Ituro、Turelli Priscilla、Trono Didier、Sato Kei
    • Journal Title

      BioRxiv

      Volume: -

    • DOI

      10.1101/2020.02.02.931501

    • Related Report
      2019 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Presentation] Sarbecovirus ORF6 proteins antagonize interferon signaling by blocking mRNA export.2021

    • Author(s)
      Izumi Kimura, Yoriyuki Konno, Daniel Sauter, Keiya Uriu, So Nakagawa, Kei Sato.
    • Organizer
      Conference on Retroviruses and Opportunistic Infections (vCROI 2021)
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Endogenous retroviruses drive KRAB zinc-finger protein family expression for tumor suppression.2020

    • Author(s)
      ○Jumpei Ito, Izumi Kimura, Kei Sato.
    • Organizer
      Cold Spring Harbor Laboratory Meeting on Transposable Elements
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Endogenous retroviruses drive KRAB zinc-finger family protein expression for tumor suppression.2020

    • Author(s)
      ○木村出海, 伊東潤平, 佐藤佳.
    • Organizer
      第20回東京大学生命科学シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] SARS-CoV-2 ORF3b is a potent interferon antagonist whose activity is further increased by a naturally occurring elongation variant.2020

    • Author(s)
      Yoriyuki Konno, Izumi Kimura, Keiya Uriu, Masaya Fukushi, Takashi Irie, Yoshio Koyanagi, So Nakagawa, ○Kei Sato.
    • Organizer
      Cold Spring Harbor Asia COVID19/SARS CoV2 Rapid Research Reports
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A novel coronavirus versus human: understanding the molecular mechanism of viral cross-species transmission.2020

    • Author(s)
      ○Kei Sato, Yoriyuki Konno, Izumi Kimura, Keiya Uriu.
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ウイルスと宿主の進化的攻防:エイズウイルス&新型コロナウイルス vs 人類2020

    • Author(s)
      ○佐藤佳, 今野順介, 木村出海, 瓜生慧也.
    • Organizer
      日本進化学会第22回大会
    • Related Report
      2020 Annual Research Report

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Published: 2019-05-29   Modified: 2024-03-26  

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