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HIV-1宿主域の分子基盤に関する基礎研究

Publicly Offered Research

Project AreaMatrix of Infection Phenomena
Project/Area Number 21022033
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe University of Tokushima

Principal Investigator

足立 昭夫  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (90127043)

Co-Investigator(Kenkyū-buntansha) 野間口 雅子  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 准教授 (80452647)
三宅 在子  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (20548622)
Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 2010: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2009: ¥3,800,000 (Direct Cost: ¥3,800,000)
Keywordsウイルス / HIV-1 / 宿主域 / 構造蛋白質 / Gag / Pol / Env / Vif
Research Abstract

HIV-1の宿主域は極めて狭く、ヒトとチンパンジーにしか感染・増殖せず、ヒトにのみエイズを発症させる。本研究は、感染個体内におけるHIV-1の複製と病原性発現機構の理解を目指し、この障壁となっているウイルス宿主域の分子基盤を解明しようとするものである。このために、本研究では、プロトタイプマカクザル指向性HIV-1から細胞馴化や遺伝子工学的改変によって得られた改良型ウイルスを系統的かつ網羅的に解析した。
我々の解析では、マカクザル(カニクイザルやアカゲザル等)細胞におけるウイルス増殖能の向上をもたらす適応変異はgag-CA、pol-INおよびenv-SU領域のものに限られていた。また、computer-assisted mutagenesisにより作製された変異のうち有効なものはgag-CA領域のみに存在していた。これらの変異(gag-8CA、pol-INおよびenv-SU領域内変異)を全て持つウイルスは細胞レベルではSIVmac239(マカクザル病原性標準株)に匹敵する増殖能を示した。これらのウイルスを用いたカニクイザルへの感染実験を共同研究として始めているが、良好な結果を得つつある。
解析した有効な変異のうち、gag-CAの全てとenv-SUの一つは宿主域に直接的に関与しているが、他の変異は細胞種に依らずウイルス複製能自体を向上させるものであった。gag-CA内変異はウイルス抑制因子であるTRIM5αと密接に関わっており、僅かなCAの構造変化がマカクザル細胞でのHIV-1複製量に大きく影響していることが明らかになった。特筆すべきことに、pol-IN領域の変異はアミノ酸ではなくコドン配列依存性の効果を示す新しいタイプのものであった。今後のウイルス学的研究の新展開が期待できる。

Report

(2 results)
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (26 results)

All 2011 2010 2009

All Journal Article (17 results) (of which Peer Reviewed: 15 results) Presentation (9 results)

  • [Journal Article] Improved capacity of a monkey-tropic HIV-1 derivative to replicate in cynomolgus monkeys with minimal modifications2011

    • Author(s)
      Akatsuki Saito
    • Journal Title

      Microbes and Infection

      Volume: 13 Pages: 58-64

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of HIV-1 Nef protein for virus replication in vitro2010

    • Author(s)
      Abhay Jere
    • Journal Title

      Microbes and Infection

      Volume: 12 Pages: 65-70

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Status of APOBEC3G/F in cells and progeny virions modulated by Vif determines HIV-1 infectivity2010

    • Author(s)
      Tomoki Yamashita
    • Journal Title

      Microbes and Infection

      Volume: 12 Pages: 166-171

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Different interaction between HIV-1 Vif and its cellular target proteins APOBEC3G/APOBEC3F2010

    • Author(s)
      Tamiko Nagao
    • Journal Title

      Journal of Medical Investigation

      Volume: 57 Pages: 89-94

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multifaceted activity of HIV Vpr/Vpx proteins : the current view of their virological functions2010

    • Author(s)
      Mikako Fujita
    • Journal Title

      Reviews in Medical Virology

      Volume: 20 Pages: 68-76

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Virology as biosystematics : towards understanding the viral infection biology2010

    • Author(s)
      Masako Nomaguchi
    • Journal Title

      Frontiers in Microbiology

      Volume: 1

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Growth ability in various macaque cell lines of HIV-1 with simian cell-tropism2010

    • Author(s)
      Naoya Doi
    • Journal Title

      Journal of Medical Investigation

      Volume: 57 Pages: 284-292

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Site-directed mutagenesis of HIV-1 vpu gene demonstrates two clusters of replication-defective mutants with distinct ability to down-modulate cell surface CD4 and tetherin2010

    • Author(s)
      Masako Nomaguchi
    • Journal Title

      Frontiers in Microbiology

      Volume: 1

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of HIV - 1 Nef protein for virus replication in vitro2010

    • Author(s)
      Abhay Jere
    • Journal Title

      Microbes and Infection 12

      Pages: 65-70

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Status of APOBEC3G/F in cells and progeny virions modulated by Vifdetermines HIV-1 infectivity2010

    • Author(s)
      Tomoki Yamashita
    • Journal Title

      Microbes and Infection 12

      Pages: 166-171

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multifaceted activity of HIV Vpr/Vpx proteins : the current view of their virological functions2010

    • Author(s)
      Mikako Fujita
    • Journal Title

      Reviews in Medical Virology 20

      Pages: 68-76

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Different interaction between HIV-1 Vif and its cellular target proteins APOBEC3G/APOBEC3F2010

    • Author(s)
      Tamiko Nagao
    • Journal Title

      Journal of Medical Investigation 57

      Pages: 89-94

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Amino acid alterations in Gag that confer the ability to grow in simian cells on HIV-1 are located at a narrow CA region2009

    • Author(s)
      Tamiko Nagao
    • Journal Title

      Journal of Medical Investigation 56

      Pages: 21-25

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evasion from CypA- and APOBEC-mediated restrictions is insufficient for HIV-1 to efficiently grow in simian cells2009

    • Author(s)
      Kazuya Kamada
    • Journal Title

      Microbes and Infection 11

      Pages: 164-171

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modification of a loop sequence beween α-helices 6 and 7 of virus capsid (CA) protein in a human immunodeficiency virus type 1 (HIV-1) derivative that has simian immunodeficiency virus (SIVmac239) vif and CA α-helices 4 and 5 loop improves replication in cynomolgus monkey cells2009

    • Author(s)
      Ayumu Kuroishi
    • Journal Title

      Retrovirology 6

      Pages: 70-70

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HIV-1の病原性:細胞から個体へ2009

    • Author(s)
      野間口雅子
    • Journal Title

      Journal of AIDS Research 11

      Pages: 94-95

    • Related Report
      2009 Annual Research Report
  • [Journal Article] アクセサリー蛋白質と抗HIV細胞因子2009

    • Author(s)
      野間口雅子
    • Journal Title

      ウイルス 59

      Pages: 67-74

    • NAID

      130004922955

    • Related Report
      2009 Annual Research Report
  • [Presentation] HIV-1宿主域を規定する細胞因子とウイルス蛋白質(シンポジウム4)2010

    • Author(s)
      足立昭夫
    • Organizer
      第24回日本エイズ学会学術集会
    • Place of Presentation
      東京都
    • Year and Date
      2010-11-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] HIV-1増殖過程におけるインテグラーゼ(IN)C末端領域(CTD)の影響2010

    • Author(s)
      三宅在子
    • Organizer
      第24回日本ウイルス学会学術集会
    • Place of Presentation
      東京都
    • Year and Date
      2010-11-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] カニクイザルTRIM5alleleがサル指向性HIV-1の増殖に与えるインパクト2010

    • Author(s)
      齊藤暁
    • Organizer
      第24回日本エイズ学会学術集会
    • Place of Presentation
      東京都
    • Year and Date
      2010-11-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] サル細胞で効率よく増殖するHIV-1の構築-アカゲザルTRIM5αとtetherinによる抑制の回避-2010

    • Author(s)
      野間口雅子
    • Organizer
      第24回日本エイズ学会学術集会
    • Place of Presentation
      東京都
    • Year and Date
      2010-11-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] サル指向性HIV-1 CAの1アミノ酸変異はサル細胞での増殖を促進する2010

    • Author(s)
      土肥直哉
    • Organizer
      第58回日本ウイルス学会学術集会
    • Place of Presentation
      徳島市
    • Year and Date
      2010-11-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] アカゲザルに存在する抗HIV-1因子TRIM5αとtetherinを回避するサル細胞指向性HIV-1の構築2010

    • Author(s)
      野間口雅子
    • Organizer
      第58回日本ウイルス学会学術集会
    • Place of Presentation
      徳島市
    • Year and Date
      2010-11-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] HIV-1インテグラーゼ(IN)C末端領域(CTD)における1塩基置換によるウイルス増殖促進機構の解析2010

    • Author(s)
      三宅在子
    • Organizer
      第58回日本ウイルス学会学術集会
    • Place of Presentation
      徳島市
    • Year and Date
      2010-11-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] Analysis of growth adaptive mutations in HIV-1 genome identifies a pol-integrase region that enhances virion production in a cell-independent and codon triplet-dependent manner2010

    • Author(s)
      Ariko Miyake
    • Organizer
      The 10th Awaji International Forum on Infection and Immunity
    • Place of Presentation
      Awaji, Japan
    • Year and Date
      2010-09-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] Modification of a loop between α-helices 6 and 7 of virus capsid protein improves human immunodeficiency virus type 1 replication in cynomolgus monkey cells2009

    • Author(s)
      Ayumu Kuroishi
    • Organizer
      The 9th Awaji International Forum on Infection and Immunity
    • Place of Presentation
      Awaji Yumebutai (Awaji, Japan)
    • Year and Date
      2009-09-10
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2018-03-28  

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