前列腺素 A1 诱导热休克蛋白 70 抑制 HIV-1 Vif 介导的 APOBEC3G 降解。

Induction of heat-shock protein 70 by prostaglandin A₁ inhibits HIV-1 Vif-mediated degradation of APOBEC3G.

机构信息

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.

出版信息

Antiviral Res. 2013 Sep;99(3):307-11. doi: 10.1016/j.antiviral.2013.06.017. Epub 2013 Jul 4.

DOI:10.1016/j.antiviral.2013.06.017

PMID:23831493

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.

摘要

先前的研究表明，环戊烯酮前列腺素（cyPGs）可抑制多种细胞类型中的人类免疫缺陷病毒 1 型（HIV-1）复制。这种抗病毒活性与感染细胞中热休克蛋白 70（HSP70）的诱导有关。我们研究了前列腺素 A₁（PGA₁）在非允许细胞中 HIV-1 复制中的新作用。由于 HSP70 的过表达通过泛素-蛋白酶体途径阻断了病毒感染性因子（Vif）介导的 APOBEC3G（A3G）降解，因此我们检查了 PGA₁对 A3G 和 HIV-1 复制的影响。PGA₁诱导 HSP70 合成可阻断 Vif 介导的 A3G 降解，并增强 A3G 掺入野生型和 Vif 缺陷型病毒中。此外，我们确定了从 PGA₁ 处理的 293T 细胞中产生的 HIV-1 颗粒的病毒滴度。在存在 A3G 的情况下，PGA₁ 诱导 HSP70 合成可显著降低病毒滴度。此外，在单次或重复用 PGA₁处理的非允许细胞中，p24 Gag 抗原水平显着降低。因此，我们表明 PGA₁ 通过阻断 Vif 介导的 A3G 降解来抑制 HIV-1 复制，至少在一定程度上如此。