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Study on molecular and structural basis of anti-retroviral activity by APOBEC3

Research Project

Project/Area Number 24590568
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Virology
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, その他 (90303403)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsウイルス / 生体分子 / 酵素 / タンパク質 / 生体防御因子 / レトロウイルス / 宿主因子 / APOBEC3 / 感染制御 / シチジンデアミナーゼ / 核酸結合 / 生化学 / HIV / 核酸結合タンパク質 / 生化学的解析
Outline of Final Research Achievements

Human APOBEC3 family proteins are powerful cellular defense factors that potently inhibit replication of retroviruses, including HIV and retrotransposons. However, some retroviruses such as HIV replicate by expressing Vif protein, which specifically eliminates the APOBEC3s' antiviral functions. In this research project, we obtained two major findings: 1) the antiviral molecular mechanisms are fundamentally linked to their homo-oligomerization capacity, which is directly correlated with affinity (dissociation constants) to single-stranded nucleic acids; 2) the Vif-binding conformations on APOBEC3C/F/D are characterized as shallow hydrophobic cavities surrounded with negatively-charged area. These data provide important and novel information to further understand the molecular mechanisms of APOBEC3s' antiviral functions.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (42 results)

All 2015 2014 2013 2012 Other

All Journal Article (16 results) (of which Peer Reviewed: 14 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (24 results) (of which Invited: 9 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Sequence and structural determinants of human APOBEC3H deaminase and anti-HIV-1 activities2015

    • Author(s)
      Mitra M, Singer D, Mano Y, Hritz J, Nam G, Gorelick RJ, Byeon IJ, Gronenborn AM, Iwatani Y, Levin JG.
    • Journal Title

      Retrovirology

      Volume: 12 Issue: 1 Pages: 3-3

    • DOI

      10.1186/s12977-014-0130-8

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] APOBEC3H polymorphisms associated with susceptibility to HIV-1 infection and AIDS progression in Japanese.2015

    • Author(s)
      Sakurai D, Iwatani Y, Ohtani H, Naruse TK, Terunuma H, Sugiura W, Kimura A.
    • Journal Title

      Immunogenetics

      Volume: 67 Issue: 4 Pages: 253-257

    • DOI

      10.1007/s00251-015-0829-2

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Japanese Drug Resistance HIVSN: Phylodynamic analysis reveals CRF01_AE dissemination between Japan and neighboring Asian countries and the role of intravenous drug use in transmission.2014

    • Author(s)
      Shiino T, Hattori J, Yokomaku Y, Iwatani Y, Sugiura W.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 7 Pages: e102633-e102633

    • DOI

      10.1371/journal.pone.0102633

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] APOBEC3 の抗ウイルス作用およびHIV-1 Vifによる分解不活化の分子メカニズム2014

    • Author(s)
      大出裕高、岩谷靖雅
    • Journal Title

      日本エイズ学会誌

      Volume: 16 Pages: 61-69

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Oligomerization transforms human APOBEC3G from an efficient enzyme to a slowly dissociating nucleic acid binding protein.2014

    • Author(s)
      Chaurasiya KR, McCauley MJ, Wang W, Qualley DF, Wu T, Kitamura S, Geertsema H, Chan DSB, Hertz A, Iwatani Y, Levin JG, Musier-Forsyth K, Rouzina I, and Williams MC.
    • Journal Title

      Nature Chemistry

      Volume: 6 Issue: 1 Pages: 28-33

    • DOI

      10.1038/nchem.1795

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lack of Association between Intact/Deletion Polymorphisms of the APOBEC3B Gene and HIV-1 Risk.2014

    • Author(s)
      Imahashi M, Izumi T, Watanabe D, Imamura J, Matsuoka K, Ode H, Masaoka T, Sato K, Kaneko N, Ichikawa S, Koyanagi Y, Takaori-Kondo A, Utsumi M, Yokomaku Y, Shirasaka T, Sugiura W, Iwatani Y, Naoe T.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 3 Pages: e92861-e92861

    • DOI

      10.1371/journal.pone.0092861

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Poly-proline motif in HIV-2 Vpx is critical for its efficient translation2014

    • Author(s)
      Ariko Miyake, Mikako Fujita, Haruna Fujino, Ryoko Koga, Sogo Kawamura, Masami Otsuka, Hirotaka Ode, Yasumasa Iwatani, Yosuke Sakai, Naoya Doi, Masako Nomaguchi, Akio Adachi, Yasuyuki Miyazaki
    • Journal Title

      Journal of General Virology

      Volume: 95 Issue: 1 Pages: 179-189

    • DOI

      10.1099/vir.0.057364-0

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Results of external quality assessment for proviral DNA testing of HIV tropism in the Maraviroc Switch collaborative study.2013

    • Author(s)
      Tu E, Swenson LC, Land S, Pett S, Emery S, Marks K, Kelleher AD, Kaye S, Kaiser R, Schuelter E, Harrigan R and the research laboratory.
    • Journal Title

      Journal of Clinical Microbiology

      Volume: 51 Issue: 7 Pages: 2063-2071

    • DOI

      10.1128/jcm.00510-13

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] TRIM5 genotypes in cynomolgus monkeys primarily influence inter-individual diversity in susceptibility to monkey-tropic human immunodeficiency virus type 12013

    • Author(s)
      Saito A, Nomaguchi M, Kono K, Iwatani Y, Yokoyama M, Yasutomi Y, Sato H, Shioda T, Sugiura W, Matano T, Adachi A, Nakayama E, Akari H
    • Journal Title

      J Gen Virol

      Volume: 94(Pt 6) Issue: 6 Pages: 1318-24

    • DOI

      10.1099/vir.0.050252-0

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Generation of rhesus macaque-tropic HIV-1 clones that are resistant to major anti-HIV-1 restriction factors2013

    • Author(s)
      Nomaguchi M, Yokoyama M, Kono K, Nakayama EE, Shioda T, Doi N, Fujiwara S, Saito A, Akari H, Miyakawa K, Ryo A, Ode H, Iwatani Y, Miura T, Igarashi T, Sato H, Adachi A
    • Journal Title

      J Virol

      Volume: 87(21) Issue: 21 Pages: 11447-11461

    • DOI

      10.1128/jvi.01549-13

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] HIV アクセサリータンパク質の機能2013

    • Author(s)
      北村紳悟、岩谷靖雅
    • Journal Title

      ウイルス

      Volume: 63 Pages: 187-198

    • NAID

      130004713424

    • Related Report
      2013 Research-status Report
  • [Journal Article] Zinc finger function of HIV-1 nucleocapsid protein is required for removal of 5´-terminal genomic RNA fragments: A paradigm for RNA removal reactions in HIV-1 reverse transcription.2013

    • Author(s)
      Hergott CB, Mitra M, Guo J, Wu T, Miller JT, Iwatani Y, Gorelick RJ, Levin JG
    • Journal Title

      Virus Research

      Volume: 171 Issue: 2 Pages: 346-355

    • DOI

      10.1016/j.virusres.2012.08.013

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular epidemiology of HIV-1 infection in Iran: genomic evidence of CRF35_AD predominance and CRF01_AE infection among individuals associated with injection drug use.2012

    • Author(s)
      Jahanbakhsh F, Ibe S, Hattori J, Monavari SHR, Matsuda M, Maejima M, Iwatani Y, Memarnejadian A, Keyvani H, Azadmanesh K, Sugiura W
    • Journal Title

      AIDS Research and Human Retroviruses

      Volume: 29 Issue: 1 Pages: 198-203

    • DOI

      10.1089/aid.2012.0186

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Association of APOBEC3G genotypes and CD4 decline in Thai and Cambodian HIV-infected children with moderate immune deficiency.2012

    • Author(s)
      Bunupuradah T, Imahashi M, Iampornsin T, Matsuoka K, Iwatani Y, Puthanakit T, Ananworanich J, Sophonphan J, Mahanontharit A, Naoe T, Vonthanak S, Phanuphak P, Sugiura W, et al.
    • Journal Title

      AIDS Research and therapy

      Volume: 9 Issue: 1 Pages: 34-34

    • DOI

      10.1186/1742-6405-9-34

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The APOBEC3C crystal structure and the interface for HIV-1 Vif binding.2012

    • Author(s)
      Kitamura S, Ode H, Nakashima M, Imahashi M, Naganawa Y, Kurosawa T, Yokomaku Y, Yamane T, Watanabe N, Suzuki A, Sugiura W, Iwatani Y
    • Journal Title

      Nature Structural and Molecular Biology

      Volume: 19 Issue: 10 Pages: 1005-1010

    • DOI

      10.1038/nsmb.2378

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Antiviral mechanism and biochemical basis of the human APOBEC3 family.2012

    • Author(s)
      Imahashi M, Nakashima M, Iwatani Y
    • Journal Title

      Frontier in Microbiology

      Volume: 2 Pages: 250-250

    • DOI

      10.3389/fmicb.2012.00250

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Vif/APOBEC3を標的とする治療薬開発2014

    • Author(s)
      岩谷靖雅
    • Organizer
      第62回日本化学療法学会西日本支部総会・第57回日本感染症学会中日本地方会学術集会・第84回日本感染症学会西日本地方会学術集会・合同開催
    • Place of Presentation
      岡山
    • Year and Date
      2014-10-23 – 2014-10-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Crystal structure of the Vif-inteaction domain of the anti-viral APOBE3F2014

    • Author(s)
      Nakashima M, Kitamura S, Kurosawa T, Ode H, Kawamura T, Imahashi Y, Yokomaku Y, Watanabe N, Sugiura W, Iwatani Y
    • Organizer
      23rd Congress and general assembly of the international union of crystallography
    • Place of Presentation
      Cold Spring Harbor, NY, USA
    • Year and Date
      2014-08-05 – 2014-08-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] HIVが抗ウイルス細胞因子APOBEC3 から逃れる分子機序2014

    • Author(s)
      岩谷靖雅
    • Organizer
      平成26年度遺伝子制御研究所研究集会・感染、免疫、炎症、発癌
    • Place of Presentation
      札幌
    • Year and Date
      2014-07-03 – 2014-07-04
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Lack of Association between Intact/Deletion Polymorphisms of the APOBEC3B Gene and HIV-1 Risk2014

    • Author(s)
      Imahashi M, Izumi T, Imamura J, Matsuoka K, Ode H, Masaoka T, Sato K, Koyanagi Y, Takaori-Kondo A, Yokomaku Y, Sugiura W, Iwatani Y
    • Organizer
      Cold Spring Harbor Laboratory Annual meeting on Retroviruses
    • Place of Presentation
      Cold Spring Harbor, NY, USA
    • Year and Date
      2014-05-19 – 2014-05-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] Fine-tuned HIV-1 Vif-interaction interface of anti-retroviral cytidine deaminase APOBEC3F2014

    • Author(s)
      Nakashima M, Kitamura S, Kurosawa T, Ode H, Kawamura T, Mano Y, Naganawa Y, Yokomaku Y, Watanabe N, Sugiura W, Iwatani Y
    • Organizer
      Cold Spring Harbor Laboratory Annual meeting on Retroviruses
    • Place of Presentation
      Cold Spring Harbor, NY, USA
    • Year and Date
      2014-05-19 – 2014-05-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] HIV-1 Invalidates Antiviral System of Cellular APOBEC3 Cytidine Deaminases2014

    • Author(s)
      Iwatani Y
    • Organizer
      7th APOCB Congress and ASCB workshop
    • Place of Presentation
      シンガポール
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Structural features of HIV-1 Vif-binding Interface on antiviral APOBEC3 proteins.2013

    • Author(s)
      Iwatani Y
    • Organizer
      The 14th KUMAMOTO AIDS Seminar
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Vif/APOBEC3を標的とする治療薬開発の戦略(Vif)2013

    • Author(s)
      岩谷靖雅
    • Organizer
      第27回日本エイズ学会学術集会・総会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] HIV-1感染伝播・病勢に対するAPOBEC3B遺伝子型の影響に関する解析2013

    • Author(s)
      岩谷靖雅
    • Organizer
      第15回白馬シンポジウム
    • Place of Presentation
      名古屋
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] APOBEC3F C末端側ドメインの構造解析とHIV-1 Vif 結合インターフェイス2013

    • Author(s)
      中島雅晶、北村紳悟、黒澤哲平、大出裕高、河村高志、今橋真弓、長縄由里子、真野由有、横幕能行、渡邉信久、杉浦 亙、岩谷靖雅
    • Organizer
      第27回日本エイズ学会学術集会・総会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] 抗HIV-1宿主因子APOBEC3FのVif 結合領域に関する構造学的解析2013

    • Author(s)
      北村紳悟、中島雅晶、黒沢哲平、大出裕高、河村高志、今橋真弓、長縄由里子、真野由有、横幕能行、渡邉信久、杉浦亙、岩谷靖雅
    • Organizer
      第61回日本ウイルス学会学術集会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report
  • [Presentation] 宿主防御因子APOBEC3Bの遺伝子欠損によるHIV-1感染伝播・病勢への影響に関する研究2013

    • Author(s)
      今橋真弓、泉泰輔、渡邊大、今村淳治、松岡和弘、正岡崇志、佐藤桂、金子典代、市川誠一、小柳義夫、高折晃史、内海眞、横幕能行、白阪琢磨、直江知樹、杉浦亙、岩谷靖雅
    • Organizer
      第61回日本ウイルス学会学術集会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report
  • [Presentation] Crystal structure of human APOBEC3C and HIV-1 Vif-binding interface2013

    • Author(s)
      Kitamura S, Ode H, Nakashima M, Imahashi M, Naganawa Y, Kurosawa T, Yokomaku Y, Yamane T, Watanabe N, Suzuki A, Sugiura W, Iwatani Y
    • Organizer
      American Crystallographic Association Annual Meeting
    • Place of Presentation
      ハワイ、米国
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒト抗レトロウイルス因子APOBEC3ファミリー間におけるHIV-1 Vif 結合インターフェイスの構造比較2013

    • Author(s)
      北村紳悟, 大出裕高, 中島雅晶, 今橋真弓, 長縄由里子, 黒沢哲平, 横幕能行, 山根隆, 渡邉信久, 鈴木淳巨, 杉浦亙, 岩谷靖雅
    • Organizer
      第13回日本蛋白質科学会年会
    • Place of Presentation
      鳥取
    • Related Report
      2013 Research-status Report
  • [Presentation] The crystal structure of APOBEC3C including HIV-1 Vif-binding interface2013

    • Author(s)
      Kitamura S, Ode H, Nakashima M, Imahashi M, Naganawa Y, Kurosawa T, Yokomaku Y, Yamane T, Watanabe N, Suzuki A, Sugiura W, Iwatani Y
    • Organizer
      4th International Symposium on Diffraction Structural Biology
    • Place of Presentation
      名古屋
    • Related Report
      2013 Research-status Report
  • [Presentation] Structure-based analysis of APOBEC3 on anti-HIV function2013

    • Author(s)
      Iwatani Y
    • Organizer
      Gordon Research Conferences (RNA editing)
    • Place of Presentation
      Galveston, TX, USA
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] The APOBEC3C crystal structure and the interface for HIV-1 Vif interaction (Talk)2012

    • Author(s)
      Kitamura S, Ode H, Nakashima M, Imahashi M, Naganawa Y, Yokomaku Y, Suzuki A, Watanabe N, Sugiura W, Iwatani Y
    • Organizer
      Cold Spring Harbor Laboratory Meeting (2012 meeting on Retroviruses)
    • Place of Presentation
      Cold Spring Harbor, NY, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] Conformational conservation of the HIV-1 Vif-binding interface of APOBEC3C, DE, F. (Poster)2012

    • Author(s)
      Kitamura S, Ode H, Nakashima M, Imahashi M, Naganawa Y, Yokomaku Y, Suzuki A, Watanabe N, Sugiura W, Iwatani Y
    • Organizer
      Cold Spring Harbor Laboratory Meeting (2012 meeting on Retroviruses)
    • Place of Presentation
      Cold Spring Harbor, NY, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] Oligomerization of HIV-1 restriction factor APOBEC3G transforms it from a fast enzyme to a slow nucleic acid binding protein. (Talk)2012

    • Author(s)
      Chaurasiya KR, Geertsema H, Qualley DF, Wu T, Iwatani Y, Chan D, Hertz A, Levin JG, Musier-Forsyth K, Rouzina I, Williams MC
    • Organizer
      Cold Spring Harbor Laboratory Meeting (2012 meeting on Retroviruses)
    • Place of Presentation
      Cold Spring Harbor, NY, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] 抗レトロウイルス因子 APOBEC3C の構造と HIV-1 Vif 結合インターフェイス2012

    • Author(s)
      北村紳悟、大出裕高、中島雅晶、今橋真弓、長縄由里子、黒沢哲平、横幕能行、渡邉信久、鈴木淳巨、杉浦亙、岩谷靖雅
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] APOBEC3Gの酵素活性非依存的な抗HIV-1 作用メカニズム2012

    • Author(s)
      岩谷靖雅、前島雅美、北村紳悟、大出裕高、中島雅晶、今橋真弓、長縄由里子、黒沢哲平、伊部史朗、横幕能行、杉浦亙
    • Organizer
      第60回日本ウイルス学会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
  • [Presentation] APOBEC3C の結晶構造解析とHIV-1 Vif 結合インターフェイスの同定.2012

    • Author(s)
      北村紳悟、大出裕高、中島雅晶、今橋真弓、長縄由里子、横幕能行、鈴木淳巨、渡邉信久、杉浦亙、岩谷靖雅
    • Organizer
      第12回日本蛋白質科学会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
  • [Presentation] 細胞防御因子 APOBEC3 を活用する抗HIV治療に向けた造学的研究2012

    • Author(s)
      岩谷靖雅
    • Organizer
      日本学術振興会回折構造生物第169委員会研究会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] APOBEC3のHIV-1 Vif 結合インターフェイス2012

    • Author(s)
      岩谷靖雅
    • Organizer
      第14回白馬シンポジウム
    • Place of Presentation
      京都
    • Related Report
      2012 Research-status Report
    • Invited
  • [Book] 最先端メディカルエンジニアリング2014

    • Author(s)
      岩谷靖雅、渡邉信久
    • Publisher
      一粒書房
    • Related Report
      2014 Annual Research Report
  • [Remarks] ライフサイエンス 新着論文レビュー

    • URL

      http://first.lifesciencedb.jp/archives/5889

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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