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Extensive studies on anti-retroviral mechanisms mediated by APOBEC3H

Research Project

Project/Area Number 19H03482
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49060:Virology-related
Research InstitutionNational Hospital Organization Nagoya Medical Center

Principal Investigator

Iwatani Yasumasa  独立行政法人国立病院機構(名古屋医療センター臨床研究センター), その他部局等, 部長 (90303403)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2020: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Keywords抗ウイルス作用 / レトロウイルス / APOBEC3H / 核酸 / 構造 / 遺伝多型 / 逆転写 / 細胞内局在 / 二本鎖RNA
Outline of Research at the Start

APOBEC3ファミリータンパク質による抗ウイルス分子機序は明らかになりつつあるが, 唯一APOBEC3Hの作用機序と細胞内制御機序の解明は大幅に遅れている。最近, 申請者らは, APOBEC3Hの分子構造を決定し, これまでの定説を覆す新たなAPOBEC3H-核酸結合様式について報告した。本研究では, この独自の新知見を生かし, APOBEC3Hによる抗レトロウイルス作用および細胞内制御の分子機序を明らかにすることを目的として本研究を行う。そして, APOBEC3ファミリーによる生体防御機構の更なる理解と, それらを活用した新たな治療戦略の創製につながる分子基盤を創出する。

Outline of Final Research Achievements

APOBEC3H is a member of the polynucleotide cytidine deaminases with potent antiviral activity against retroviruses. In this project, we aimed to solve molecular mechanisms of antiretroviral activity and intracellular targeting/localization of APOBEC3H. We found that one of the unique APOBEC3H’s biochemical functions, i.e., dimerization/multimerization mediated by double-stranded RNA (dsRNA), is fundamentally involved in their mechanisms. In addition, our study revealed that APOBEC3H mutants deficient in the dsRNA binding (including natural human variants) are specifically degraded through a ubiquitination/proteasome degradation machinery.

Academic Significance and Societal Importance of the Research Achievements

APOBEC3HはHIVなどのレトロウイルス感染の抵抗性に関わる抗ウイルス因子であり、その効果には遺伝多型による人種差があることが知られている。本研究成果は、遺伝多型がどのような機序で効果に差が生じるのかを理解する知見となる。そのため、HIVなどのレトロウイルスの世界的な感染伝播の方向性などの理解につながる基盤となる。さらに、本研究成果は、宿主ゲノムの損傷機序にも関連していたため、癌研究分野などにも波及する重要な知見であると考えられる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (31 results)

All 2022 2021 2020 2019

All Journal Article (18 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 18 results,  Open Access: 14 results) Presentation (13 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results)

  • [Journal Article] SARS-CoV-2 accessory protein ORF8 is secreted extracellularly as a glycoprotein homodimer2022

    • Author(s)
      Matsuoka K, Imahashi N, Ohno M, Ode H, Nakata Y, Kubota M, Sugimoto A, Imahashi M, Yokomaku Y, Iwatani Y
    • Journal Title

      Journal of Biological Chemistry

      Volume: 298 Issue: 3 Pages: 101724-101724

    • DOI

      10.1016/j.jbc.2022.101724

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular epidemiological features of SARS-CoV-2 in Japan, 2020?12022

    • Author(s)
      Ode Hirotaka、Nakata Yoshihiro、Nagashima Mami、Hayashi Masaki、Yamazaki Takako、Asakura Hiroyuki、Suzuki Jun、Kubota Mai、Matsuoka Kazuhiro、Matsuda Masakazu、Mori Mikiko、Sugimoto Atsuko、Imahashi Mayumi、Yokomaku Yoshiyuki、Sadamasu Kenji、Iwatani Yasumasa
    • Journal Title

      Virus Evolution

      Volume: 8 Issue: 1

    • DOI

      10.1093/ve/veac034

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Monobodies with potent neutralizing activity against SARS-CoV-2 Delta and other variants of concern2022

    • Author(s)
      Kondo Taishi、Matsuoka Kazuhiro、Umemoto Shun、Fujino Tomoshige、Hayashi Gosuke、Iwatani Yasumasa、Murakami Hiroshi
    • Journal Title

      Life Science Alliance

      Volume: 5 Issue: 6 Pages: e202101322-e202101322

    • DOI

      10.26508/lsa.202101322

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Specific mutations in the HIV-1 G-tract of the 3′-polypurine tract cause resistance to integrase strand transfer inhibitors2021

    • Author(s)
      Hachiya Atsuko、Kubota Mai、Shigemi Urara、Ode Hirotaka、Yokomaku Yoshiyuki、Kirby Karen A、Sarafianos Stefan G、Iwatani Yasumasa
    • Journal Title

      Journal of Antimicrobial Chemotherapy

      Volume: 77 Issue: 3 Pages: 574-577

    • DOI

      10.1093/jac/dkab448

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Retrospective Analysis of the Efficacy of Early Antiretroviral Therapy in HIV-1-Infected Patients Coinfected with <i>Pneumocystis jirovecii</i>2021

    • Author(s)
      Kasahara Takaaki、Imahashi Mayumi、Hashiba Chieko、Mori Mikiko、Kogure Ayumi、Yokomaku Yoshiyuki、Hashimoto Naozumi、Iwatani Yasumasa、Hasegawa Yoshinori
    • Journal Title

      AIDS Research and Human Retroviruses

      Volume: 37 Issue: 10 Pages: 754-760

    • DOI

      10.1089/aid.2021.0025

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The FAT10 Posttranslational Modification Is Involved in Lytic Replication of Kaposi’s Sarcoma-Associated Herpesvirus2021

    • Author(s)
      Sugimoto Atsuko、Abe Yuichi、Watanabe Tadashi、Hosokawa Kohei、Adachi Jun、Tomonaga Takeshi、Iwatani Yasumasa、Murata Takayuki、Fujimuro Masahiro
    • Journal Title

      Journal of Virology

      Volume: 95 Issue: 10 Pages: 02194-20

    • DOI

      10.1128/jvi.02194-20

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cytokines and Chemokines Involved in Hepatitis B Surface Antigen Loss in Human Immunodeficiency Virus/Hepatitis B Virus Coinfected Patients2021

    • Author(s)
      Urata Noboru、Watanabe Tsunamasa、Hirashima Noboru、Yokomaku Yoshiyuki、Imamura Junji、Iwatani Yasumasa、Shimada Masaaki、Tanaka Yasuhito
    • Journal Title

      Journal of Clinical Medicine

      Volume: 10 Issue: 4 Pages: 833-833

    • DOI

      10.3390/jcm10040833

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SARS-CoV-2 D614G spike mutation increases entry efficiency with enhanced ACE2-binding affinity2021

    • Author(s)
      Ozono Seiya、Zhang Yanzhao、Ode Hirotaka、Sano Kaori、Tan Toong Seng、Imai Kazuo、Miyoshi Kazuyasu、Kishigami Satoshi、Ueno Takamasa、Iwatani Yasumasa、Suzuki Tadaki、Tokunaga Kenzo
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 848-848

    • DOI

      10.1038/s41467-021-21118-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of long-term antiretroviral therapy on gut and oral microbiotas in HIV-1-infected patients2021

    • Author(s)
      Imahashi Mayumi、Ode Hirotaka、Kobayashi Ayumi、Nemoto Michiko、Matsuda Masakazu、Hashiba Chieko、Hamano Akiko、Nakata Yoshihiro、Mori Mikiko、Seko Kento、Nakahata Masashi、Kogure Ayumi、Tanaka Yasuhito、Sugiura Wataru、Yokomaku Yoshiyuki、Iwatani Yasumasa
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 960-960

    • DOI

      10.1038/s41598-020-80247-8

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Antibody-like proteins that capture and neutralize SARS-CoV-22020

    • Author(s)
      Kondo T.、Iwatani Y.、Matsuoka K.、Fujino T.、Umemoto S.、Yokomaku Y.、Ishizaki K.、Kito S.、Sezaki T.、Hayashi G.、Murakami H.
    • Journal Title

      Science Advances

      Volume: 6 Issue: 42 Pages: 3916-3916

    • DOI

      10.1126/sciadv.abd3916

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The 4th and 112th Residues of Viral Capsid Cooperatively Modulate Capsid-CPSF6 Interactions of HIV-12020

    • Author(s)
      Saito Akatsuki、Sultana Tahmina、Ode Hirotaka、Nohata Kyotaro、Samune Yoshihiro、Nakayama Emi E.、Iwatani Yasumasa、Shioda Tatsuo
    • Journal Title

      AIDS Research and Human Retroviruses

      Volume: 36 Issue: 6 Pages: 513-521

    • DOI

      10.1089/aid.2019.0250

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HIV-1陽性検体を用いたAlinity mシステムによるHIV-1ウイルスの核酸定量検査の検討2020

    • Author(s)
      蜂谷敦子,今橋真弓,岩谷靖雅,横幕能行
    • Journal Title

      医学と薬学

      Volume: 77 Pages: 1443-1448

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prevalence of HIV-1 Integrase Polymorphisms and Drug Resistance Mutations in Newly Diagnosed Individuals with HIV-1 in the Tokai Area2019

    • Author(s)
      SHIGEMI U、OKAZAKI R、ODE H、MATSUDA M、KUBOTA Mi、YANO K、TSURUMI H、OKUMURA N、TANIGUCHI H、SHICHI D、IKEGAYA T、ITO M、MATSUMOTO T、KURAI H、KAWABATA A、HASHIBA C、NAKAHATA M、KOGURE A、HATTORI J、IBE S、IMAHASHI M、IWATANI Y、SUGIURA W、YOSHIMURA K、HACHIYA A、YOKOMAKU Y
    • Journal Title

      Kansenshogaku Zasshi

      Volume: 93 Issue: 3 Pages: 312-318

    • DOI

      10.11150/kansenshogakuzasshi.93.312

    • NAID

      130007761511

    • ISSN
      0387-5911, 1884-569X
    • Year and Date
      2019-05-20
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Trends in Transmitted Drug Resistance and Prevalence of Non-B Subtype in Newly Diagnosed Individuals with HIV-1 in the Tokai Area2019

    • Author(s)
      OKAZAKI R、SHIGEMI U、MATSUDA M、KUBOTA M、YANO K、TSURUMI H、OKUMURA N、TANIGUCHI H、SHICHI D、IKEGAYA T、ITO M、MATSUMOTO T、KURAI H、KAWABATA A、HASHIBA C、NAKAHATA M、KOGURE A、HATTORI J、IBE S、IMAHASHI M、IWATANI Y、SUGIURA W、YOSHIMURA K、HACHIYA A、YOKOMAKU Y
    • Journal Title

      Kansenshogaku Zasshi

      Volume: 93 Issue: 3 Pages: 298-305

    • DOI

      10.11150/kansenshogakuzasshi.93.298

    • NAID

      130007761515

    • ISSN
      0387-5911, 1884-569X
    • Year and Date
      2019-05-20
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid2019

    • Author(s)
      Sultana Tahmina*、Mamede Joao I.*、Saito Akatsuki*、Ode Hirotaka、Nohata Kyotaro、Cohen Romy、Nakayama Emi E.、Iwatani Yasumasa、Yamashita Masahiro、Hope Thomas J.、Shioda Tatsuo
    • Journal Title

      Journal of Virology

      Volume: 93 Issue: 23 Pages: 1-27

    • DOI

      10.1128/jvi.00986-19

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] HIV-1 is more dependent on the K182 capsid residue than HIV-2 for interactions with CPSF62019

    • Author(s)
      Saito Akatsuki、Ode Hirotaka、Nohata Kyotaro、Ohmori Hisaki、Nakayama Emi E.、Iwatani Yasumasa、Shioda Tatsuo
    • Journal Title

      Virology

      Volume: 532 Pages: 118-126

    • DOI

      10.1016/j.virol.2019.04.012

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identifying integration sites of the HIV-1 genome with intact and aberrant ends through deep sequencing2019

    • Author(s)
      Ode Hirotaka、Kobayashi Ayumi、Matsuda Masakazu、Hachiya Atsuko、Imahashi Mayumi、Yokomaku Yoshiyuki、Iwatani Yasumasa
    • Journal Title

      Journal of Virological Methods

      Volume: 267 Pages: 59-65

    • DOI

      10.1016/j.jviromet.2019.03.004

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pre-treatment and acquired HIV drug resistance in Dar es Salaam, Tanzania in the era of tenofovir and routine viral load monitoring2019

    • Author(s)
      Barabona Godfrey、Mahiti Macdonald、Masoud Salim、Mbelele Peter、Mgunya Amina Shaban、Minja Lilian、Sunguya Bruno、Shigemi Urara、Matsuda Masakazu、Hachiya Atsuko、Iwatani Yasumasa、Lyamuya Eligius、Ueno Takamasa
    • Journal Title

      Journal of Antimicrobial Chemotherapy

      Volume: 74 Issue: 10 Pages: 3016-3020

    • DOI

      10.1093/jac/dkz272

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Antiretroviral molecular mechanisms of APOBEC3 cytidine deaminases2021

    • Author(s)
      Yasumasa Iwatani
    • Organizer
      22nd Kumamoto AIDS Seminar
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] SARS-CoV-2に対する人工中和抗体の開発2021

    • Author(s)
      岩谷靖雅
    • Organizer
      日本薬学会 第141年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 新しいARTに向けた創薬基礎研究の進展状況 HIVアクセサリータンパク質を標的とした新規治療法開発2020

    • Author(s)
      岩谷靖雅
    • Organizer
      第34回 日本エイズ学会学術集会・総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 国内のHIV-2精査検体を用いた、HIV診断におけるGeenius HIV1/2 Confirmatory Assayの有用性についての検討2020

    • Author(s)
      重見麗, 山村喜美, 松田昌和, 岡﨑玲子, 久保田舞, 齋藤誠司, 栁澤邦雄, 柳 富子, 伊部史郎, 根本理子, 前島雅美, 助川明香, 今橋真弓, 杉浦亙, 岩谷靖雅, 蜂谷敦子, 横幕能行
    • Organizer
      第34回 日本エイズ学会学術集会・総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 当院におけるPCP発症AIDSに対する早期ART導入の臨床的検討2020

    • Author(s)
      笠原嵩翔, 三輪紀子, 羽柴知恵子, 森美貴子, 林雅, 今橋真弓, 小暮あゆみ, 横幕能行, 岩谷靖雅
    • Organizer
      第34回 日本エイズ学会学術集会・総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] これからの季節に備えた新型コロナウイルスとPCR検査2020

    • Author(s)
      岩谷靖雅
    • Organizer
      第45回 日本口腔外科学会中部支部学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 高速液体クロマトグラフィー-蛍光検出器による第二世代HIVインテグラーゼ阻害剤の血中濃度測定法の確立2019

    • Author(s)
      中田佳宏, 松岡和弘, 平野淳, 大出裕高, 今橋真弓, 蜂谷敦子, 中井正彦, 横幕能行, 岩谷靖雅
    • Organizer
      第33回日本エイズ学会学術集会・総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] in vivo passageで獲得したサル馴化HIV-1のvif遺伝子領域における欠損変異の役割2019

    • Author(s)
      松岡和弘, 中田佳宏, 鷲﨑彩夏, 芳田剛, 齊藤暁, 関洋平, 大出裕高, 蜂谷敦子, 保富康宏, 原田恵嘉, 石井洋, 俣野哲朗, 三浦智行, 佐藤賢文, 明里宏文, 岩谷靖雅
    • Organizer
      第33回日本エイズ学会学術集会・総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Comparative analyses of primate antiviral APOBEC3C2019

    • Author(s)
      Nakashima M, Ode H, Hamano A, Nakata Y, Matsuoka K, Sukegawa S, Hachiya A, Imahashi M, Watanabe N, Yokomaku Y, Iwatani Y
    • Organizer
      Cold spring harbor laboratory meeting on retroviruses
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒト免疫不全ウイルス ―細胞防御酵素とHIVによる逃避のしくみ―2019

    • Author(s)
      岩谷靖雅
    • Organizer
      日本パスツール財団セミナーシリーズ1「ウイルスの構造と機能
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Biochemical characteristics of ARIH2 in HIV-1 Vif mediated APOBEC3-ubiquitination2019

    • Author(s)
      松岡和弘、大出裕高、中田佳宏、蜂谷敦子、今橋真弓、横幕能行、岩谷靖雅
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Structural Interference of Polymorphic R105G in Antiviral APOBEC3H2019

    • Author(s)
      大出裕高、中田佳宏、松岡和弘、今橋真弓、蜂谷敦子、横幕能行、岩谷靖雅
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] HIV-1 Vif C-TERMINAL region plays a critical role in the ANTAGONISM OF ANTIVIRAL APOBEC3 FUNCTION2019

    • Author(s)
      Yasumasa Iwatani、Kazuhiro Matsuoka、Akiko Hamano、Hirotaka Ode、Yoshihiro Nakata、Sayaka Sukegawa、Atsuko Hachiya、Mayumi Imahashi、Yoshiyuki Yokomaku
    • Organizer
      38th Annual American Society for Virology Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2023-01-30  

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