Identification of host factors cleaved by HIV protease for elucidating the mechanism of innate immune evasion.

• Project/Area Number: 16H07105
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Virology
• Research Institution: Yokohama City University
• Principal Investigator: MATSUNAGA Satoko 横浜市立大学, 医学部, 助教 (20779342)
• Project Period (FY): 2016-08-26 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: HIV / プロテアーゼ / 自然免疫 / 細胞死 / ウイルス / 宿主因子

Outline of Final Research Achievements

In this study, we investigated the cleavage of host factors related to innate immune response by HIV protease (HIV-PR). We identified 4 host substrates being cleaved by HIV-PR using in in vitro assay system with recombinant proteins. Among them, we selected CASP1 since it is a key factor for pyroptotic cell death. We confirmed that HIV protease cleaved CASP1 in cells leading to the secretion of intracellular LDH to extracellular space due to the cell membrane damage. We also found that a protease inhibitor DRV specifically suppressed the CASP1 cleavage and resultant cell toxicity by HIV-PR. These results indicate a possibility that HIV-1 protease is involved in the pyroptotic cell death mediated CASP1.

Research Products

• [Int'l Joint Research] ミシガン大学(米国)
• [Int'l Joint Research] シンガポール国際大学(シンガポール)
• [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] Lyn Kinase Suppresses the Transcriptional Activity of IRF5 in the TLR-MyD88 Pathway to Restrain the Development of Autoimmunity. (2016)
  • Author(s): Ban T., Sato G.R., Nishiyama A., Akiyama A., Takasuna M., Umehara M., Suzuki S., Ichino M., Matsunaga S., Kimura A., Kimura Y., Yanai H., Miyashita S., Kuromitsu J., Tsukahara K., Yoshimatsu K., Endo I., Yamamoto T., Hirano H., Ryo A., Taniguchi T., Tamura T.
  • Journal Title: Immunity Volume: 45 Issue: 2 Pages: 319-332
  • DOI: 10.1016/j.immuni.2016.07.015
  • 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] Protein Active Arrayを用いたヒト血清中に含まれる抗ウイルス抗体の網羅的検出 (2017)
  • Author(s): 松永智子, 松島勇紀, 森下了, 木村博一, 梁明秀
  • Organizer: 第65回日本ウイルス学会学術集会
• [Remarks] 横浜市立大学大学院微生物学・分子生体防御学
  • URL: http://www-user.yokohama-cu.ac.jp/~saikin/