APOBEC3G and APOBEC3F require an endogenous cofactor to block HIV-1 replication
APOBEC3G and APOBEC3F require an endogenous cofactor to block HIV-1 replication
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DOI：
10.1371/journal.ppat.1000095
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发表时间：
2008-07-01
期刊：
影响因子：
6.7
通讯作者：
Zheng, Yong-Hui
中科院分区：
文献类型：
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作者：
Han, Yanxing;Wang, Xiaojun;Zheng, Yong-Hui
APOBEC3G (A3G)/APOBEC3F （A3F）是APOBEC3胞苷脱氨酶亚家族的两个成员。尽管它们能有效地抑制vif缺陷HIV-1的复制，但这一机制仍然知之甚少。最初，A3G/A3F被认为在逆转录过程中催化负链病毒cdna上的C-to-U转变，从而破坏病毒的生命周期。最近，人们发现A3G/A3F更有可能直接阻断病毒的逆转录或整合。此外，A3G/A3F都存在于永生化细胞系的高分子质量复合体中，在那里它们与许多不同的细胞蛋白相互作用。然而，没有证据证明这些相互作用是A3G/A3F功能所必需的。在这里，我们研究了A3G/ a3f限制HIV-1在六种不同的人类T细胞系中的复制，方法是用野生型或vif缺陷型HIV-1感染它们。有趣的是，在表达高水平A3G/A3F蛋白的CEM-T4细胞系中，vif缺陷病毒的复制与野生型病毒一样好，这表明这些内源性抗逆转录病毒基因失去了抗hiv活性。经证实，这些A3G/A3F基因不含任何突变，功能正常。同样，外源性A3G/A3F在CEM-T4细胞中过表达仍然不能恢复其抗hiv活性。然而，如果CEM-T4细胞与293T细胞融合形成异核体，这种活性可以恢复。这些结果表明CEM-T4细胞缺乏对A3G/A3F抗hiv活性至关重要的细胞辅助因子。我们建议对这一新因子的进一步研究将为全面了解A3G/A3F抗逆转录病毒机制提供另一种策略。
APOBEC3G (A3G)/APOBEC3F (A3F) are two members of APOBEC3 cytidine deaminase subfamily. Although they potently inhibit the replication of vif-deficient HIV-1, this mechanism is still poorly understood. Initially, A3G/A3F were thought to catalyze C-to-U transitions on the minus-strand viral cDNAs during reverse transcription to disrupt the viral life cycle. Recently, it was found more likely that A3G/A3F directly interrupts viral reverse transcription or integration. In addition, A3G/A3F are both found in the high-molecular-mass complex in immortalized cell lines, where they interact with a number of different cellular proteins. However, there has been no evidence to prove that these interactions are required for A3G/A3F function. Here, we studied A3G/A3F-restricted HIV-1 replication in six different human T cell lines by infecting them with wild-type or vif-deficient HIV-1. Interestingly, in a CEM-derived cell line CEM-T4, which expresses high levels of A3G/A3F proteins, the vif-deficient virus replicated as equally well as the wild-type virus, suggesting that these endogenous antiretroviral genes lost anti-HIV activities. It was confirmed that these A3G/A3F genes do not contain any mutation and are functionally normal. Consistently, overexpression of exogenous A3G/A3F in CEM-T4 cells still failed to restore their anti-HIV activities. However, this activity could be restored if CEM-T4 cells were fused to 293T cells to form heterokaryons. These results demonstrate that CEM-T4 cells lack a cellular cofactor, which is critical for A3G/A3F anti-HIV activity. We propose that a further study of this novel factor will provide another strategy for a complete understanding of the A3G/A3F antiretroviral mechanism.