Induction of heat-shock protein 70 by prostaglandin A₁ inhibits HIV-1 Vif-mediated degradation of APOBEC3G.
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.
['Sugiyama|Ryuichi|R|', 'Abe|Makoto|M|', 'Nishitsuji|Hironori|H|', 'Murakami|Yuko|Y|', 'Takeuchi|Hiroaki|H|', 'Takaku|Hiroshi|H|']
D000071480:APOBEC-3G Deaminase D019380:Anti-HIV Agents D002460:Cell Line D003564:Cytidine Deaminase D015536:Down-Regulation D015658:HIV Infections D015497:HIV-1 D018840:HSP70 Heat-Shock Proteins D006801:Humans D011454:Prostaglandins A D059748:Proteolysis D015854:Up-Regulation D014779:Virus Replication D054320:vif Gene Products, Human Immunodeficiency Virus
Heat-shock protein Human immunodeficiency virus Antiviral Viral infectivity factor APOBEC3G Prostaglandin A(1)