Heat Shock Protein 70 Inhibits HIV-1 Vif-mediated Ubiquitination and Degradation of APOBEC3G*
Heat Shock Protein 70 Inhibits HIV-1 Vif-mediated Ubiquitination and Degradation of APOBEC3G*
复制标题
DOI：
10.1074/jbc.m110.166108
复制
发表时间：
2011-01
期刊：
影响因子：
--
通讯作者：
Ryuichi Sugiyama;H. Nishitsuji;A. Furukawa;M. Katahira;Y. Habu;H. Takeuchi;A. Ryo;H. Takaku
中科院分区：
文献类型：
--
作者：
Ryuichi Sugiyama;H. Nishitsuji;A. Furukawa;M. Katahira;Y. Habu;H. Takeuchi;A. Ryo;H. Takaku
胞苷脱氨酶APOBEC 3G，这是纳入新生的病毒颗粒，具有强大的抗病毒活性，并限制在逆转录步骤中通过脱氨依赖性和非依赖性的影响，Vf-缺陷型HIV-1的复制。HIV-1 Vif通过诱导APOBEC 3G多聚泛素化及其随后的蛋白酶体降解来抵消APOBEC 3G的抗病毒活性。在这项研究中，我们表明，热休克蛋白70（HSP 70）的过表达阻断了APOBEC 3G在泛素-蛋白酶体途径的HIV-1 Vif的降解，使病毒颗粒非感染性。此外，siRNA靶向敲低HSP 70表达增强了Vif介导的APOBEC 3G降解。一项免疫共沉淀研究显示，HSP 70的过表达抑制了APOBEC 3G与HIV-1 Vif的结合。因此，我们提供了宿主蛋白介导的抑制HIV-1复制的APOBEC 3G依赖的方式的证据。
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.