Identification of host factors associated with persistent transactivation of HIV

• Project/Area Number: 15K19117
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: Microbial Chemistry Research Foundation
• Principal Investigator: ISHIZAKA Aya 公益財団法人微生物化学研究会, 微生物化学研究所, 博士研究員 (70746859)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: HIV / 残存感染細胞 / 免疫活性化 / 潜伏感染

Outline of Final Research Achievements

In this study, we identified prematurely terminated short HIV-1 transcripts (STs) in peripheral blood mononuclear cells as an efficient intracellular biomarker to monitor viral activation and immune status in patients with cART-mediated full viral suppression in plasma. The levels of STs strongly reflected chronic immune activation. These observations represent evidence for a relationship between viral persistence and host immune activation, which in turn results in the suboptimal increase in CD4+ cells despite suppressive antiretroviral therapy. This cell-based measurement of viral persistence contributes to an improved understanding of the dynamics of viral persistence in patients.

Research Products

• [Journal Article] Transferrin Receptor 1 Facilitates Poliovirus Permeation of Mouse Brain Capillary Endothelial Cells. (2016)
  • Author(s): Mizutani T, Ishizaka A, Nihei C.
  • Journal Title: Journal of Biological Chemistry Volume: 291 Issue: 6 Pages: 2829-2836
  • DOI: 10.1074/jbc.m115.690941
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Short intracellular HIV-1 transcripts as biomarkers of residual immune activation in patients on antiretroviral therapy. (2016)
  • Author(s): A. Ishizaka, H. Sato, H. Nakamura, M. Koga, T. Kikuchi, N. Hosoya, T. Koibuchi, A. Nomoto, A. Kawana-Tachikawa and T. Mizutani
  • Journal Title: Journal of Virology Volume: 未確定 Issue: 12 Pages: 5665-76
  • DOI: 10.1128/jvi.03158-15
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The Werner Protein Acts as a Coactivator of Nuclear Factor κB (NF-κB) on HIV-1 and Interleukin-8 (IL-8) Promoters (2015)
  • Author(s): Mizutani T, Ishizaka A, Furuichi Y
  • Journal Title: The Journal of Biological Chemistry Volume: 290 Issue: 30 Pages: 18391-18399
  • DOI: 10.1074/jbc.m115.657155
  • Peer Reviewed
• [Presentation] Cell associated HIV RNA (Short Transcripts)とT細胞活性化との関連 (2016)
  • Author(s): 石坂彩、佐藤秀憲、中村仁美、古賀道子、鯉渕智彦、立川（川名）愛、水谷壮利
  • 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（鹿児島県鹿児島市）
  • Year and Date: 2016-11-25
• [Presentation] Short intracellular HIV-1 transcripts serve as biomarkers of residual immune activation in patients on antiretroviral therapy (2016)
  • Author(s): Aya Ishizaka, Hidenori Sato, Hitomi Nakamura, Michiko Koga, Tomohiko Koibuchi, Ai Kawana-Tachikawa and Taketoshi Mizutani
  • Organizer: 2nd Kumamoto IRCMS International Symposium and 17th Kumamoto AIDS Seminar
  • Place of Presentation: くまもと県民交流館パレア（熊本県熊本市）
  • Year and Date: 2016-10-31
  • Int'l Joint Research
• [Remarks] 微生物化学研究会 微生物化学研究所
  • URL: http://www.bikaken.or.jp/research/publications/index.php
• [Remarks] 公益財団法人 微生物化学研究会 微生物化学研究所
  • URL: http://www.bikaken.or.jp/
• [Patent(Industrial Property Rights)] 免疫状態の判定方法、ＣＤ４＋Ｔ細胞数の増加予測方法、 及びＣＤ４＋Ｔ細胞数の減少予測方法、並びにそれらのためのキット (2015)
  • Inventor(s): 水谷壮利、石坂彩、立川愛
  • Industrial Property Rights Holder: 公益財団法人 微生物化学研究会
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-10-07
  • Overseas