title: Induction of heat-shock protein 70 by prostaglandin A₁ inhibits HIV-1 Vif-mediated degradation of APOBEC3G.
abstract: Previous studies have demonstrated that cyclopentenone prostaglandins (cyPGs) inhibit human immunodeficiency virus type 1 (HIV-1) replication in various cell types. This antiviral activity has been associated with the induction of heat-shock protein 70 (HSP70) in infected cells. We investigated a new role of prostaglandin A₁ (PGA₁) in the replication of HIV-1 in non-permissive cells. Because overexpression of HSP70 blocks the viral infectivity factor (Vif)-mediated degradation of APOBEC3G (A3G) via the ubiquitin-proteasome pathway, we examined the effects of PGA₁ on A3G and HIV-1 replication. The induction of HSP70 synthesis by PGA₁ blocked Vif-mediated A3G degradation and enhanced the incorporation of A3G into both wild-type and Vif-deficient viruses. Furthermore, we determined the viral titer of HIV-1 particles produced from PGA₁-treated 293T cells. The induction of HSP70 synthesis by PGA₁ significantly reduced the viral titer in the presence of A3G. Additionally, the p24 Gag antigen levels were dramatically reduced in non-permissive cells treated once or repeatedly with PGA₁. Thus, we showed that PGA₁ inhibits HIV-1 replication, at least in part, by blocking Vif-mediated A3G degradation.
authors.affiliation: Department of Life and Environmental Sciences, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan; Department of Virology II, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Sugiyama
authors.forename: Makoto
authors.initials: M
authors.lastname: Abe
authors.forename: Hironori
authors.initials: H
authors.lastname: Nishitsuji
authors.forename: Yuko
authors.initials: Y
authors.lastname: Murakami
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takaku
mesh_terms: D000071480:APOBEC-3G Deaminase; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D011454:Prostaglandins A / Q000494:pharmacology*; D059748:Proteolysis / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D019380:Anti-HIV Agents; D018840:HSP70 Heat-Shock Proteins; D011454:Prostaglandins A; D054320:vif Gene Products, Human Immunodeficiency Virus; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase; C100573:prostaglandin A1
keywords: APOBEC3G; Antiviral; Heat-shock protein; Human immunodeficiency virus; Prostaglandin A(1); Viral infectivity factor