Identification of novel, interferon-inducible anti-AIDS virus host factors

• Project/Area Number: 17K15701
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: Osaka University
• Principal Investigator: Saito Akatsuki 大阪大学, 微生物病研究所, 特任助教(常勤) (30621792)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 宿主因子 / エイズウイルス / インターフェロン / HIV / ウィルス / エイズ

Outline of Final Research Achievements

In this research project, we sought to identify a novel, type I IFN-inducible anti-HIV host factors in T cells. We performed RNA-Seq analysis using samples of two T cell lines that showed distinct antiviral effect upon IFN treatment. We identified doses of candidate genes upregulated in a cell line that strongly inhibit HIV infection upon IFN treatment. We used the CRISPR-Cas9 system to knockout candidate genes. Our results showed that gene depletion of known antiviral host factors diminished antiviral effect upon IFN treatment. Further screening of candidate genes is now in progress.

Academic Significance and Societal Importance of the Research Achievements

これまで、我々を含む国内外の研究グループにより、未同定のIFN誘導性のエイズウイルス感染阻害因子が存在することが示唆されている。近年のオミックス研究の飛躍的な進歩により、遺伝子発現レベルの網羅的解析が比較的容易になってきてはいるが、適切なコントロールがない場合、莫大な量のデータから目的遺伝子を特定するのは容易ではない。我々が今回行ったRNA-Seq実験では、IFN処理によりHIV感染を阻害する細胞でのみ発現レベルが上昇する遺伝子を効率よく抽出できた。現在限られた数の候補遺伝子の評価を進めており、長年解明が求められていたエイズウイルス抑制因子の解明に貢献していきたい。

Research Products

• [Int'l Joint Research] Northwestern University(米国)
• [Journal Article] CA Mutation N57A Has Distinct Strain-Specific HIV-1 Capsid Uncoating and Infectivity Phenotypes. (2019)
  • Author(s): Douglas K. Fischer, Akatsuki Saito, Christopher Kline, Romy Cohen, Simon C. Watkins, Masahiro Yamashita, Zandrea Ambrose
  • Journal Title: Journal of Virology Volume: 印刷中 Issue: 9
  • DOI: 10.1128/jvi.00214-19
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Naturally Occurring Mutations in HIV-1 CRF01_AE Capsid Affect Viral Sensitivity to Restriction Factors (2018)
  • Author(s): Nakayama Emi E.、Saito Akatsuki、Sultana Tahmina、Jin Zhuan、Nohata Kyotaro、Shibata Masato、Hosoi Miho、Motomura Kazushi、Shioda Tatsuo、Sangkitporn Somchai、Loket Ruangchai、Saeng-aroon Siriphan
  • Journal Title: AIDS Research and Human Retroviruses Volume: 34 Issue: 4 Pages: 382-392
  • DOI: 10.1089/aid.2017.0212
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Human T-cell leukemia virus type 1 infects multiple lineage hematopoietic cells in vivo (2017)
  • Author(s): Furuta Rie、Yasunaga Jun-ichirou、Miura Michi、Sugata Kenji、Saito Akatsuki、Akari Hirofumi、Ueno Takaharu、Takenouchi Norihiro、Fujisawa Jun-ichi、Koh Ki-Ryang、Higuchi Yusuke、Mahgoub Mohamed、Shimizu Masakazu、Matsuda Fumihiko、Melamed Anat、Bangham Charles R.、Matsuoka Masao
  • Journal Title: PLOS Pathogens Volume: 13 Issue: 11 Pages: 1-22
  • DOI: 10.1371/journal.ppat.1006722
  • NAID: 120006697285
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Multiple pathways to avoid IFN-β sensitivity of HIV-1 by mutants in capsid (2018)
  • Author(s): Akatsuki Saito, Joao I. Mamede, Tahmina Sultana, Hirotaka Ode, Yasumasa Iwatani, Emi E. Nakayama, Thomas J. Hope, Tatsuo Shioda
  • Organizer: The 43rd annual meeting on Retroviruses, Cold Spring Harbor Meeting
  • Int'l Joint Research
• [Presentation] The Q4R mutation specifically accelerates kinetics of reverse transcription and initiation of uncoating of IFN-β hypersensitive HIV-1 capsid mutant (2018)
  • Author(s): Akatsuki Saito, Joao I. Mamede, Tahmina Sultana, Kyotaro Nohata, Emi E nakayama, Tatsuo Shioda, Thomas J Hope
  • Organizer: 第66回日本ウイルス学会学術集会
  • Int'l Joint Research
• [Presentation] HIV-1カプシドによるI型インターフェロン感受性の制御 (2018)
  • Author(s): 齊藤暁
  • Organizer: 第32回日本エイズ学会学術集会
  • Invited
• [Presentation] カプシド182番目アミノ酸残基のCPSF6結合への寄与はHIV-1とHIV-2で異なる (2018)
  • Author(s): 齊藤暁, 大出裕高, 野畑享太郎, 大森久樹, 中山英美, 岩谷靖雅, 塩田達雄
  • Organizer: 第32回日本エイズ学会学術集会
• [Presentation] Mutations in viral capsid modulate IFN-β sensitivity of HIV-1 (2018)
  • Author(s): Akatsuki Saito, Joao I. Mamede, Tahmina Sultana, Hirotaka Ode, Yasumasa Iwatani, Emi E. Nakayama, Tatsuo Shioda, Thomas J. Hope
  • Organizer: U.S.-Japan Cooperative Medical Sciences Program (USJCMSP) 20th International Conference on Emerging Infectious Diseases (EID) in the Pacific Rim (AIDS and Immunology Joint Panel)
  • Int'l Joint Research
• [Presentation] Mutations in viral capsid modulate IFN-β sensitivity of HIV-1 (2018)
  • Author(s): Akatsuki Saito, Joao I. Mamede, Tahmina Sultana, Hirotaka Ode, Yasumasa Iwatani, Emi E. Nakayama, Tatsuo Shioda, Thomas J. Hope
  • Organizer: U.S.-Japan Cooperative Medical Sciences Program (USJCMSP) 20th International Conference on Emerging Infectious Diseases (EID) in the Pacific Rim
  • Int'l Joint Research / Invited
• [Presentation] カプシド領域の変異は HIV-1 の IFN 感受性を制御する (2017)
  • Author(s): 齊藤 暁、Tahmina Sultana、大出裕高、岩谷靖雅、中山英美、塩田達雄
  • Organizer: 第31回日本エイズ学会学術集会
• [Presentation] Mutations in viral capsid modulate IFN-β sensitivity of HIV-1 (2017)
  • Author(s): Tahmina Sultana, Akatsuki Saito, Hirotaka Ode, Yasumasa Iwatani, Emi E. Nakayama, Tatsuo Shioda
  • Organizer: 第65回日本ウイルス学会学術集会
• [Presentation] Mutations in viral capsid modulate IFN-β sensitivity of HIV-1 (2017)
  • Author(s): Akatsuki Saito, Tahmina Sultana, Hirotaka Ode, Yasumasa Iwatani, Emi E. Nakayama, Tatsuo Shioda
  • Organizer: 第16回あわじしま感染症・免疫フォーラム
  • Int'l Joint Research