HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracellular stability
HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracellular stability
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DOI：
10.1016/s1097-2765(03)00353-8
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发表时间：
2003-09-01
期刊：
影响因子：
16
通讯作者：
Greene, WC
中科院分区：
文献类型：
--
作者：
Stopak, K;de Noronha, C;Greene, WC
人类免疫缺陷病毒1型（HIV-1）依赖Vif（病毒感染因子）来克服APOBEC 3G（载脂蛋白B mRNA编辑酶，催化多肽样3G，也称为CEM 15）的强效抗病毒功能。使用APOBEC 3G特异性抗血清，我们现在表明，Vif通过有效地消耗HIV-1感染的T细胞中这种酶的细胞内水平来防止内源性APOBEC 3G的病毒粒子掺入。Vif通过损害APOBEC 3G mRNA的翻译和加速26 S蛋白酶体对APOBEC 3G蛋白的翻译后降解来实现这种消耗。Vif与APOBEC 3G物理相互作用，并且在不存在其他HIV-1蛋白的情况下单独表达Vif足以引起APOBEC 3G的消耗。这些发现强调了Vif对APOBEC 3G的双峰翻译和翻译后抑制作用如何结合联合收割机，以显著抑制这种有效的抗病毒酶在病毒感染细胞中的表达，从而有效地减少APOBEC 3G掺入新形成的HIV-1病毒粒子。
The human immunodeficiency virus type 1 (HIV-1) relies on Vif (viral infectivity factor) to overcome the potent antiviral function of APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G, also known as CEM15). Using an APOBEC3G-specific antiserum, we now show that Vif prevents virion incorporation of endogenous APOBEC3G by effectively depleting the intracellular levels of this enzyme in HIV-1-infected T cells. Vif achieves this depletion by both impairing the translation of APOBEC3G mRNA and accelerating the posttranslational degradation of the APOBEC3G protein by the 26S proteasome. Vif physically interacts with APOBEC3G, and expression of Vif alone in the absence of other HIV-1 proteins is sufficient to cause depletion of APOBEC3G. These findings highlight how the bimodal translational and posttranslational inhibitory effects of Vif on APOBEC3G combine to markedly suppress the expression of this potent antiviral enzyme in virally infected cells, thereby effectively curtailing the incorporation of APOBEC3G into newly formed HIV-1 virions.