Department of Life and Environmental Sciences, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan.
J Biol Chem. 2011 Mar 25;286(12):10051-7. doi: 10.1074/jbc.M110.166108. Epub 2011 Jan 12.
The cytidine deaminase APOBEC3G, which is incorporated into nascent virus particles, possesses potent antiviral activity and restricts Vif-deficient HIV-1 replication at the reverse transcription step through deamination-dependent and -independent effects. HIV-1 Vif counteracts the antiviral activity of APOBEC3G by inducing APOBEC3G polyubiquitination and its subsequent proteasomal degradation. In this study, we show that overexpression of heat shock protein 70 (HSP70) blocked the degradation of APOBEC3G in the ubiquitin-proteasome pathway by HIV-1 Vif, rendering the viral particles non-infectious. In addition, siRNA targeted knock-down of HSP70 expression enhanced the Vif-mediated degradation of APOBEC3G. A co-immunoprecipitation study revealed that overexpression of HSP70 inhibited APOBEC3G binding to HIV-1 Vif. Thus, we provide evidence for a host protein-mediated suppression of HIV-1 replication in an APOBEC3G-dependent manner.
细胞嘧啶脱氨酶 APOBEC3G 整合到新生病毒颗粒中，具有强大的抗病毒活性，并通过脱氨酶依赖和非依赖的效应限制逆转录步骤中 Vif 缺陷的 HIV-1 复制。HIV-1 Vif 通过诱导 APOBEC3G 多泛素化及其随后的蛋白酶体降解来拮抗 APOBEC3G 的抗病毒活性。在这项研究中，我们表明，热休克蛋白 70（HSP70）的过表达通过 HIV-1 Vif 阻断了泛素-蛋白酶体途径中 APOBEC3G 的降解，使病毒颗粒失去感染性。此外，siRNA 靶向敲低 HSP70 表达增强了 Vif 介导的 APOBEC3G 降解。共免疫沉淀研究表明，HSP70 的过表达抑制了 APOBEC3G 与 HIV-1 Vif 的结合。因此，我们提供了宿主蛋白介导的 HIV-1 复制抑制的证据，这种抑制是 APOBEC3G 依赖的方式。
