HIV latency by the change of microenvironment

• Project/Area Number: 16K08814
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: Yokohama City University
• Principal Investigator: MIYAKAWA Kei 横浜市立大学, 医学部, 講師 (20580046)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: HIV潜伏化 / HIV再活性化 / latency-reversing agents / HIV潜伏・再活性化 / 低酸素

Outline of Final Research Achievements

The availability of highly effective anti-retroviral drugs has nearly suppressed the progression of HIV infection to AIDS. However, the reactivation of the virus upon discontinuation of medication is a major problem, as these therapeutic agents can not eliminate latently infected cells. The detailed mechanisms involved in HIV latency and reactivation still remain unknown. In this study, we established model cells capable of quantifying the transcriptional activity of HIV and aimed to elucidate the molecular mechanisms involved in HIV reactivation and latency. In this study, we found the involvement of central nervous signaling in HIV reactivation. We also identified two host factors involved in HIV latency. The scope of this study could be extended to develop novel therapeutic agents against HIV latency in the future.

Academic Significance and Societal Importance of the Research Achievements

HIV潜伏化や再活性化メカニズムが解明されることで、エイズ発症を防止する従来の治療から、エイズ克服にむけた治療法の開発に貢献できる可能性がある。本研究ではHIV潜伏化に関与する宿主因子を複数同定したことから、今後これらの因子に対する標的薬開発を行う予定である。

Research Products

• [Int'l Joint Research] University of Michigan Medical School(米国)
• [Int'l Joint Research] National University of Singapore,(シンガポール)
• [Journal Article] PIM kinases facilitate lentiviral evasion from SAMHD1 restriction via Vpx phosphorylation (2019)
  • Author(s): Miyakawa Kei、Matsunaga Satoko、Yokoyama Masaru、Nomaguchi Masako、Kimura Yayoi、Nishi Mayuko、Kimura Hirokazu、Sato Hironori、Hirano Hisashi、Tamura Tomohiko、Akari Hirofumi、Miura Tomoyuki、Adachi Akio、Sawasaki Tatsuya、Yamamoto Naoki、Ryo Akihide
  • Journal Title: Nature Communications Volume: 10 Issue: 1 Pages: 1844-1844
  • DOI: 10.1038/s41467-019-09867-7
  • NAID: 120006949469
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Development of a cell-based assay to identify hepatitis B virus entry inhibitors targeting the sodium taurocholate cotransporting polypeptide (2018)
  • Author(s): Miyakawa Kei、Matsunaga Satoko、Yamaoka Yutaro、Dairaku Mina、Fukano Kento、Kimura Hirokazu、Chimuro Tomoyuki、Nishitsuji Hironori、Watashi Koichi、Shimotohno Kunitada、Wakita Takaji、Ryo Akihide
  • Journal Title: Oncotarget Volume: 9 Issue: 34 Pages: 23681-23694
  • DOI: 10.18632/oncotarget.25348
  • Peer Reviewed / Open Access
• [Journal Article] がん抑制遺伝子産物APCはHIV細胞-細胞間感染を促進する. (2017)
  • Author(s): 宮川 敬, 梁 明秀
  • Journal Title: 感染・炎症・免疫 Volume: 4 Pages: 302-304
• [Journal Article] The tumour suppressor APC promotes HIV-1 assembly via interaction with Gag precursor protein. (2017)
  • Author(s): Miyakawa K, Nishi M, Matsunaga S, Okayama A, Anraku M, Kudoh A, Hirano H, Kimura H, Morikawa Y, Yamamoto N, Ono A, Ryo A.
  • Journal Title: Nature Communications Volume: 8 Issue: 1 Pages: 14259-14259
  • DOI: 10.1038/ncomms14259
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] H11/HSPB8 Restricts HIV-2 Vpx to Restore the Anti-Viral Activity of SAMHD1. (2016)
  • Author(s): Kudoh A, Miyakawa K, Matsunaga S, Matsushima Y, Kosugi I, Kimura H, Hayakawa S, Sawasaki T, Ryo A.
  • Journal Title: Frontiers in Microbiology Volume: 7 Pages: 883-883
  • DOI: 10.3389/fmicb.2016.00883
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] HIV-1複製後期過程におけるGag-CAリンカードメインの役割 (2018)
  • Author(s): 駒貴明、小谷治、土肥直哉、宮川敬、梁明秀、横山勝、佐藤裕徳、足立昭夫、野間口雅子
  • Organizer: 第66回日本ウイルス学会学術集会
• [Presentation] The tumor suppressor APC promotes HIV-1 assembly via interaction with Gag protein (2018)
  • Author(s): Miyakawa K, Ryo A
  • Organizer: U.S.-Japan Cooperative Medical Sciences Program 20th International Conference On Emerging Infectious Diseases In The Pacific Rim
  • Int'l Joint Research / Invited
• [Presentation] 宿主因子APCによるHIV細胞-細胞間伝播制御機構の解明 (2017)
  • Author(s): 宮川 敬, 梁 明秀
  • Organizer: 第31回 日本エイズ学会学術集会
• [Presentation] ケミカルバイオロジーを用いたHIV再活性化のメカニズム解析 (2016)
  • Author(s): 岩瀬早織, 宮川 敬, 工藤あゆみ, 梁 明秀
  • Organizer: 第30回日本エイズ学会学術集会
  • Place of Presentation: かごしま県民交流センター（鹿児島）
  • Year and Date: 2016-11-24
• [Presentation] NanoBRET法を用いた生細胞内HIV-1 Gagの多量体化解析および結合宿主因子探索 (2016)
  • Author(s): 宮川 敬, 松山慎一郎, 村上 努, 梁 明秀
  • Organizer: 第30回日本エイズ学会学術集会
  • Place of Presentation: かごしま県民交流センター（鹿児島）
  • Year and Date: 2016-11-24
• [Presentation] Identification of a host factor that restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction (2016)
  • Author(s): Miyakawa K, Matsunaga S, Kudoh A, Ryo A
  • Organizer: 26th ECCMID
  • Place of Presentation: RAI Amsterdam, Netherland
  • Year and Date: 2016-04-09
  • Int'l Joint Research
• [Remarks] 横浜市立大学医学部微生物学ホームページ
  • URL: http://www-user.yokohama-cu.ac.jp/~saikin/