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2007 Fiscal Year Final Research Report Summary

Molecular and virological analysis of simian and human cell-tropic HIV-1

Research Project

Project/Area Number 18390140
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionThe University of Tokushima

Principal Investigator

ADACHI Akio  The University of Tokushima, Graduate School Institute of Health Biosciences, Professor (90127043)

Co-Investigator(Kenkyū-buntansha) UCHIYAMA Tsuneo  The University of Tokushima, Graduate School Institute of Health Biosciences, Associate professor (90151901)
YAMASHITA Tomoki  The University of Tokushima, Graduate School Institute of Health Biosciences, Assistant Professor (70380087)
NOMAGUCHI Masako  The University of Tokushima, Graduate School Institute of Health Biosciences, Assistant Professor (80452647)
Project Period (FY) 2006 – 2007
KeywordsHIV-1 / SIVmac / Gag-CA / Vif / CVp3 A / TRIM5 a / APOBEC / Monkey-tropism
Research Abstract

HIV-I possesses a tightly restricted species tropism, and is pathogenic only for humans. It has been, therefore, impossible to perform the animal experiments critical for studies on highly pathogenic viruses such as HIV-1. We recently have successfully constructed a monkey-tropic HIV-I for the first time in the world. This virus has the SIV homologues of HIV-1 CypA-binding region in Gag-CA and Vif. In this research project, we aimed at : 1. determination of genomic regions responsible for monkey cell tropism, 2. elucidation of the mechanism for monkey cell tropism, 3. generation and characterization of virus clones that are adapted to grow well in monkey cells, 4. generation of monkey cell-tropic R5 viruses, 5. generation and characterization of mutants of accessory genes. A prototype monkey-tropic HIV-1 (X4) was found to infect pig-tailed and cynomolgus monkeys and to induce immunological reactions. However, it grew more poorly than the pathogenic standard SIVmac in monkey cells and in animals. A growth-defect of this virus concerning TRIM5α-restriction was successfully repaired considerably by altering a region in Gag-CA to improve its growth ability in monkey cells. We also have obtained cell-adapted virus clones (X4 and R5) with replication potentials similar to that of SIVmac. We finally generated proviral molecular clones which carry all the mutations described above, and mutants of accessory genes derived from them. We are now ready to perform animal experiments for various HIV-1/AIDS studies on basic (underlying mechanisms for viral replication and pathogenicity ; in vivo roles of accessory proteins) and clinical issues.

  • Research Products

    (44 results)

All 2008 2007 2006

All Journal Article (23 results) (of which Peer Reviewed: 11 results) Presentation (20 results) Book (1 results)

  • [Journal Article] Species barrier of HIV-1 and its jumping by virus engineering2008

    • Author(s)
      Nomaguchi, M.
    • Journal Title

      Reviews in Medical Virology (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Role of HIV-1 Vpu protein for virus spread and pathogenesis2008

    • Author(s)
      Nomaguchi, M.
    • Journal Title

      Microbes and Infection (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Vpx is critical for the reverse transcription of human immunodeficiency virus type 2 genome in macrophages2008

    • Author(s)
      Fujita, M.
    • Journal Title

      Journal of Virology (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Species barrier of HIV-1 and its jumping by virus engineering2008

    • Author(s)
      Nomaguchi, M
    • Journal Title

      Reviews in Medical Virology (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Role of HIV-1 Vpu protein for virus spread and pathogenesis2008

    • Author(s)
      Nomaguchi, M
    • Journal Title

      Microbes and Infection (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Vpx is critical for the reverse transcription of human immunodeficiency virus type 2 genome in macrophages2008

    • Author(s)
      Fujita, M
    • Journal Title

      Journal of Virology (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Generation and characterization of APOBEC3G-positive 293T cells for HIV-1 Vif study2007

    • Author(s)
      Piroozmand, A.
    • Journal Title

      Journal of Medical Investigation 54

      Pages: 154-158

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] An HIV-1 derivative with 7% SIV genetic content is able to establish infections in pig-tailed macaques2007

    • Author(s)
      Igarashi, T.
    • Journal Title

      Journal of Virology 81

      Pages: 11549-11552

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] HIV-1の病原性とアクセサリー遺伝子2007

    • Author(s)
      足立昭夫
    • Journal Title

      蛋白質核酸酵素 52

      Pages: 1261-1267

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Generation and characterization of APOBEC3G-positive 293T cells for HIV-1 Vff study2007

    • Author(s)
      Piroozmand, A
    • Journal Title

      Journal of Medical Investigation 54

      Pages: 154-158

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] An HIV-1 derivative with 7% SW genetic content is able to establish infections in pig-tailed macaques2007

    • Author(s)
      Igarashi, T
    • Journal Title

      Journal of Virology 81

      Pages: 11549-11552

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Functional roles of HIV-1 accessory genes for its pathogenicity2007

    • Author(s)
      Adachi, A
    • Journal Title

      Protein, Nucleic Acid and Protease 52

      Pages: 1261-1267

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Comparative study on the structure and cytopathogenic activity of HIV Vpr/Vpx proteins2006

    • Author(s)
      Khamsri, B.
    • Journal Title

      Microbes and Infection 8

      Pages: 10-15

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Construction of gag-chimeric viruses between HIV-1 and SIVmac that are capable of productive multi-cycle infection2006

    • Author(s)
      Kamada, K.
    • Journal Title

      Microbes and Infection 8

      Pages: 1075-1081

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Morphological study on biologically distinct vpx/vpr mutants of HIV-22006

    • Author(s)
      Piroozmand, A.
    • Journal Title

      Journal of Medical Invextigation 53

      Pages: 271-276

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Effects of lysine to arginine mutations in HIV-1 Vif on its on its expression and viral infectivity2006

    • Author(s)
      Khamsri, B.
    • Journal Title

      International Journal of Molecular Medicine 18

      Pages: 679-683

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Generation of HIV-1 derivatives that productively infect macaque monkey lymphoid cells2006

    • Author(s)
      Kamada, K.
    • Journal Title

      Proceedings of the National Academy of Sciences USA 103

      Pages: 16959-16964

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Comparative study on the structure and cytopathogenic activity of HIV Vpr/Vpx proteins2006

    • Author(s)
      Khamsri, B
    • Journal Title

      Microbes and Infection 8

      Pages: 10-15

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Construction of gag-chimeric viruses between HIV-1 and SIVmac that are capable of productive multi-cycle infection2006

    • Author(s)
      Kamada, K
    • Journal Title

      Microbes and Infection 8

      Pages: 1075-1081

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Morphological study on biologically distinct vpx/vpr mutants of HIV-22006

    • Author(s)
      Piroozmand, A
    • Journal Title

      Journal of Medical Investigation 53

      Pages: 271-276

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effects of lysine to arginine mutations in HIV-1 Vif on its on its expression and viral infectivity2006

    • Author(s)
      Khamsri, B
    • Journal Title

      International Journal of Molecular Medicine 18

      Pages: 679-683

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Generation of HIV-1 derivatives that productively infect macaque monkey lymphoid cells2006

    • Author(s)
      Kamada, K
    • Journal Title

      Proceedings of the National Academy of Sciences USA 103

      Pages: 16959-16964

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cycrophilin and HIV-12006

    • Author(s)
      Adachi, A
    • Journal Title

      Iyaku Journal Co., Ltd., Osaka

      Pages: 206-214

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] HIV-1の種特異的増殖2007

    • Author(s)
      足立 昭夫
    • Organizer
      第21回 日本エイズ学会
    • Place of Presentation
      広島市
    • Year and Date
      2007-11-29
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Species-specific replication of HIV-12007

    • Author(s)
      Adachi, A
    • Organizer
      The Japanese Society for AIDS Research
    • Place of Presentation
      Hiroshima
    • Year and Date
      2007-11-29
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 粒子放出能に関するVpuの点変異体解析2007

    • Author(s)
      野間 口雅子
    • Organizer
      第21回 日本エイズ学会
    • Place of Presentation
      広島市
    • Year and Date
      2007-11-28
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Mutational analysis of HIV-1 Vpu with respect to the virion release2007

    • Author(s)
      Nomaguchi, M
    • Organizer
      The Japanese Society for AIDS Research
    • Place of Presentation
      Hiroshima
    • Year and Date
      2007-11-28
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] HIV-1 DTクローンの細胞および個体レベルでの増殖能2007

    • Author(s)
      足立 昭夫
    • Organizer
      第55回 日本ウイルス学会
    • Place of Presentation
      札幌市
    • Year and Date
      2007-10-22
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Growth potentials in vitro and in vivo of HIV-1 DT clones2007

    • Author(s)
      Adachi, A
    • Organizer
      The Japanese Society for Virology
    • Place of Presentation
      Sapporo
    • Year and Date
      2007-10-22
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] HIV-1 Vifと宿主因子APOBEC3Fとの結合機能部位の解析2007

    • Author(s)
      山下 知輝
    • Organizer
      第55回 日本ウイルス学会
    • Place of Presentation
      札幌市
    • Year and Date
      2007-10-21
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] HIV-1 Vif種特異性決定領域の解析とサル感染性HIV-1作製への応用2007

    • Author(s)
      八町 和樹
    • Organizer
      第55回 日本ウイルス学会
    • Place of Presentation
      札幌市
    • Year and Date
      2007-10-21
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Region in HIV-1 Vif critical for its binding to APOBEC3F2007

    • Author(s)
      Yamashita, T
    • Organizer
      The Japanese Society for Virology
    • Place of Presentation
      Sapporo
    • Year and Date
      2007-10-21
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Determinants of HIV-1 genome on species tropism and generation of simian tropic HIV-12007

    • Author(s)
      Hatcho, K
    • Organizer
      The Japanese Society for Virology
    • Place of Presentation
      Sapporo
    • Year and Date
      2007-10-21
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Generation and characterization of monkey-tropic HIV-1:evasion from antiviral factors2007

    • Author(s)
      Akio Adachi
    • Organizer
      The 7th Awaji International Forum on Infection and Immunity
    • Place of Presentation
      Awaji,Japan
    • Year and Date
      2007-09-02
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Generation and characterization of monkey-tropic HIV-1 : evasion from antiviral factors2007

    • Author(s)
      Adachi, A
    • Organizer
      The 7th Awaji International Forum on Infection and Immunity
    • Place of Presentation
      Awaji, Japan
    • Year and Date
      2007-09-02
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] HIV-2 Vpxの機能領域解析2006

    • Author(s)
      藤田 美歌子
    • Organizer
      第20回 日本エイズ学会
    • Place of Presentation
      東京都
    • Year and Date
      2006-12-02
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Functional region analysis of HIV-2 Vpx2006

    • Author(s)
      Fujita, M
    • Organizer
      The Japanese Society for AIDS Research
    • Place of Presentation
      Tokyo
    • Year and Date
      2006-12-02
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] HIV-1 Vifと宿主因子APOBEC3Gとの結合機能部位の解析2006

    • Author(s)
      山下 知輝
    • Organizer
      第54回 日本ウイルス学会
    • Place of Presentation
      名古屋市
    • Year and Date
      2006-11-19
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] マクロファージでのゲノム逆転写/核移行過程におけるHIV-1 VprとHIV-2 Vpxの役割の相違2006

    • Author(s)
      藤田 美歌子
    • Organizer
      第54回 日本ウイルス学会
    • Place of Presentation
      名古屋市
    • Year and Date
      2006-11-19
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] The Vpu 124 D and RK30AA mutations impair virus release from infected macrophages2006

    • Author(s)
      Boonruang Khamsri
    • Organizer
      第54回 日本ウイルス学会
    • Place of Presentation
      名古屋市
    • Year and Date
      2006-11-19
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Region in HIV-1 Vif critical for its binding to APOBEC3G2006

    • Author(s)
      Yamashita, T
    • Organizer
      The Japanese Society for Virology
    • Place of Presentation
      Nagoya
    • Year and Date
      2006-11-19
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Distinct roles of HIV-1 Vpr and HIV-2 Vpx in the processes of reverse transcription and nuclear import of viral genome in macrophages2006

    • Author(s)
      Fujita, M
    • Organizer
      The Japanese Society for Virology
    • Place of Presentation
      Nagoya
    • Year and Date
      2006-11-19
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] The Vpu 124 D and RK3OAA mutations impair virus release from infected macrophages2006

    • Author(s)
      Khamsri, B
    • Organizer
      The Japanese Society for Virology
    • Place of Presentation
      Nagoya
    • Year and Date
      2006-11-19
    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] 免疫の進化-シクロスポリン20年の軌跡:シクロフィリンとHIV-12006

    • Author(s)
      足立 昭夫
    • Total Pages
      206-214
    • Publisher
      医薬ジャーナル社
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2010-02-04  

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