Identification and characterization of Vpx-interacting host factors

• Project/Area Number: 24790447
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: Yokohama City University
• Principal Investigator: MIYAKAWA Kei 横浜市立大学, 医学部, 助教 (20580046)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 翻訳後修飾 / 免疫応答

Research Abstract

HIV-2/SIVsm Vpx promotes the viral replication through the degradation of a host antiviral factor, SAMHD1, in myeloid cells. Although it has been reported that phosphorylation status of SAMHD1 was important for its antiviral activity, it is still unknown whether the phosphorylation of Vpx contributes its anti-SAMHD1 activity. In this study we identified several human kinases as potential host factors to interact with Vpx. Further biochemical analysis uncovered that one kinase directly interacted with Vpx and promoted its phosphorylation. This phosphorylation is found to be important on the degradation of SAMHD1 as well as efficient viral infection. Our results together suggest that a kinase we identified could regulate the Vpx-dependent viral replication.

Research Products

• [Journal Article] The phosphorylation of HIV-1 Gag by atypical protein kinase C facilitates viral infectivity by promoting Vpr incorporation into virions. (2014)
  • Author(s): Kudoh A, Takahama S, Sawasaki T, Ode H, Yokoyama M, Okayama A, Ishikawa A, Miyakawa K, Matsunaga S, Kimura H, Sugiura W, Sato H, Hirano H, Ohno S, Yamamoto N, Ryo A
  • Journal Title: Retrovirology Volume: 11 Issue: 1 Pages: 9-9
  • DOI: 10.1186/1742-4690-11-9
  • Peer Reviewed / Open Access
• [Journal Article] Generation of rhesus macaque-tropic HIV-1 clones that are resistant to major anti-HIV-1 restriction factors (2013)
  • Author(s): Nomaguchi M, Yokoyama M, Kono K, Nakayama EE, Shioda T, Doi N, Fujiwara S, Saito A, Akari H, Miyakawa K, Ryo A, Ode H, Iwatani Y, Miura T, Igarashi T, Sato H, Adachi A
  • Journal Title: J Virol Volume: 87(21) Issue: 21 Pages: 11447-11461
  • DOI: 10.1128/jvi.01549-13
  • Peer Reviewed
• [Journal Article] Interferon-induced SCYL2 limits release of HIV-1 by triggering PP2A-mediated dephosphorylation of the viral protein Vpu. (2012)
  • Author(s): Miyakawa K., et al.,
  • Journal Title: Sci Signal. Volume: 5 Issue: 245
  • DOI: 10.1126/scisignal.2003212
  • Peer Reviewed
• [Presentation] Identification and characterization of Vpx-interacting host protein kinases (2013)
  • Author(s): Miyakawa K, Matsunaga S, Kudoh A, Ryo A
  • Organizer: CSHL Retrovirus
  • Place of Presentation: ニューヨーク
• [Presentation] Vpxのリン酸化はHIV感染を制御する (2013)
  • Author(s): 宮川敬、松永智子、工藤あゆみ、梁明秀
  • Organizer: 第27回日本エイズ学会学術総会
  • Place of Presentation: 熊本
• [Presentation] HIV-1 Vif-APOBEC3Gの相互作用を調節する新規宿主因子の同定 (2013)
  • Author(s): 宮川敬、森下了、道場生基、松永智子、工藤あゆみ、高折晃史、梁明秀
  • Organizer: 第26回日本エイズ学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Vpxのリン酸化はHIV感染を制御する (2013)
  • Author(s): 宮川敬、松永智子、工藤あゆみ、梁明秀
  • Organizer: 第27回日本エイズ学会学術総会
  • Place of Presentation: 市民会館崇城大学ホール（熊本県熊本市）
• [Presentation] HIV-1 Vif-APOBEC3Gの相互作用を調節する新規宿主因子の同定 (2012)
  • Author(s): 宮川 敬
  • Organizer: 日本エイズ学会
  • Place of Presentation: 慶応義塾大学（神奈川県）