Functional analysis of HIV-1 integrase that involves in various steps of viral replication

• Project/Area Number: 22790434
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Virology
• Research Institution: The University of Tokushima
• Principal Investigator: MIYAKE Ariko 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): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ウイルス / HIV-1 / Pol-IN

Research Abstract

Analysis of adaptive mutations in macaque cell-tropic HIV-1 has shown that these alterations cluster in the C-terminal portion of integrase-coding region in the viral genome. Even a synonymous mutation was found to have a growth-enhancing effect. This effect was due to the enhanced expression of Gag and Gag-Pol proteins. Extensive analysis of the C-terminal integrase region has revealed that synonymous mutations generate both positive and negative effects on viral replication. It is thus evident that this integrase region modulates viral replication ability.

Research Products

• [Journal Article] Structural dynamics of retroviral genome and the packaging (2011)
  • Author(s): Miyazaki, Y., Miyake, A., Nomaguchi, M., and Adachi, A
  • Journal Title: Frontiers in Microbiology Volume: 2 Pages: 264-264
  • DOI: 10.3389/fmicb.2011.00264
  • Peer Reviewed
• [Journal Article] Inhibition of active HIV-1 replication by NF-κB inhibitor DHMEQ (2010)
  • Author(s): Miyake, A., Ishida, T., Yamagishi, M., Hara, T., Umezawa, K., Watanabe, T., and Horie, R.
  • Journal Title: Microbes and Infection Volume: 12 Pages: 400-408
  • Peer Reviewed
• [Journal Article] Different interaction between HIV-1 Vif and its cellular target proteins APOBEC3G/ APOBEC3F (2010)
  • Author(s): Nagao, T., Yamashita, T., Miyake, A., Uchiyama, T., Nomaguchi, M., and Adachi, A.
  • Journal Title: Journal of Medical Investigation Volume: 57 Pages: 89-94
  • NAID: 130004465205
  • Peer Reviewed
• [Journal Article] Status of APOBEC3G/ F in cells and progeny virions modulated by Vif determines HIV-1 infectivity (2010)
  • Author(s): Yamashita, T., Nomaguchi, M., Miyake, A., Uchiyama, T., and Adachi, A.
  • Journal Title: Microbes and Infectio Volume: 12 Pages: 166-171
  • Peer Reviewed
• [Presentation] A novel antisense RNA of HIV-1 ale, functions as a self-limiting factor for the HIV-1 infection (2011)
  • Author(s): Kobayashi-Ishihara, M., Yamagishi, M., Hara, T., Matsuda, Y., Miyake, A., Nakano, K., Ishida, T., Watanabe, T.
  • Organizer: XV International Congress of Virology
  • Place of Presentation: Sapporo Convention Center(Sapporo, Japan)
  • Year and Date: 2011-09-13
• [Presentation] A novel antisense RNA of HIV-1, ale, functions as a self-limiting factor for the HIV-1 infection (2011)
  • Author(s): Mie Kobayashi-Ishihara
  • Organizer: XV International Congress of Virology
  • Place of Presentation: Sapporo Convention Center (Sapporo, Japan)
  • Year and Date: 2011-09-13
• [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、齊藤暁、明里宏文、土肥直哉、藤原佐知、三宅在子、横山勝、大出裕高、佐藤裕徳、足立昭夫
  • Organizer: 第24回日本エイズ学会学術集会
  • Place of Presentation: グランドプリンスホテル高輪(東京)
  • Year and Date: 2010-11-24
• [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、土肥直哉、藤原佐知、足立昭夫、野間口雅子
  • Organizer: 第24回日本エイズ学会学術集会
  • Place of Presentation: グランドプリンスホテル高輪(東京)
  • Year and Date: 2010-11-24
• [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回日本エイズ学会
  • Place of Presentation: グランドプリンス高輪(東京都)
  • Year and Date: 2010-11-24
• [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、土肥直哉、藤原佐知、三宅在子、横山勝、大出裕高、佐藤裕徳、足立昭夫
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島県郷土文化会館(徳島)
  • Year and Date: 2010-11-08
• [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、齊藤暁、明里宏文、藤原佐知、三宅在子、横山勝、大出裕高、佐藤裕徳、足立昭夫、野間口雅子
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島県郷土文化会館(徳島)
  • Year and Date: 2010-11-08
• [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、土肥直哉、藤原佐知、足立昭夫、野間口雅子
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島県郷土文化会館(徳島)
  • Year and Date: 2010-11-07
• [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
  • Place of Presentation: あわぎんホール(徳島県)
  • Year and Date: 2010-11-07
• [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 manner (2010)
  • Author(s): Miyake, A., Doi, N., Fujiwara, S., Adachi, A., and Nomaguchi, M.
  • Organizer: The 10th Awaji International Forum on Infection and Immunity
  • Place of Presentation: Awaji Yumebutai International Conference Center(Awaji, Japan)
  • Year and Date: 2010-09-09
• [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 manner (2010)
  • Author(s): 三宅在子
  • Organizer: 第10回あわじしま感染症・免疫フォーラム
  • Place of Presentation: 淡路夢舞台国際会議場(兵庫県)
  • Year and Date: 2010-09-08