Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts
Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts
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DOI：
10.1038/nature01709
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发表时间：
2003-07-03
期刊：
影响因子：
64.8
通讯作者：
Trono, D
中科院分区：
文献类型：
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作者：
Mangeat, B;Turelli, P;Trono, D
病毒复制通常需要克服固有的细胞内防线，这一任务通常由专门的病毒基因产物完成。人类免疫缺陷病毒（HIV）的病毒体感染因子（Vif）蛋白在病毒产生的晚期阶段是对抗APOBEC 3G（载脂蛋白B mRNA编辑酶，催化多肽样3G;也称为CEM 15）抗病毒活性所必需的，APOBEC 3G是一种在人类T淋巴细胞中显著表达的蛋白（1-4）。当在APOBEC 3G存在下产生时，vif缺陷型病毒是无感染性的。APOBEC 3G与APOBEC 1密切相关，APOBEC 1是RNA编辑复合物的中心组分，可使apoB信使RNA中的胞嘧啶残基脱氨基（5-7）。APOBEC家族成员也通过dC脱氨基作用具有有效的DNA突变活性（8）;然而，APOBEC 3G的编辑潜力是否与HIV抑制相关尚不清楚。在这里，我们证明了它确实如此，因为APOBEC 3G在逆转录过程中发挥其抗病毒作用，触发新生逆转录病毒DNA中的G到A超突变。我们还发现，APOBEC 3G可以作用于除HIV外的多种逆转录病毒，这表明通过编辑的超突变是针对这一重要病原体组的一般先天防御机制。
Viral replication usually requires that innate intracellular lines of defence be overcome, a task usually accomplished by specialized viral gene products. The virion infectivity factor (Vif) protein of human immunodeficiency virus (HIV) is required during the late stages of viral production to counter the antiviral activity of APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G; also known as CEM15), a protein expressed notably in human T lymphocytes(1-4). When produced in the presence of APOBEC3G, vif-defective virus is non-infectious. APOBEC3G is closely related to APOBEC1, the central component of an RNA-editing complex that deaminates a cytosine residue in apoB messenger RNA(5-7). APOBEC family members also have potent DNA mutator activity through dC deamination(8); however, whether the editing potential of APOBEC3G has any relevance to HIV inhibition is unknown. Here, we demonstrate that it does, as APOBEC3G exerts its antiviral effect during reverse transcription to trigger G-to-A hypermutation in the nascent retroviral DNA. We also find that APOBEC3G can act on a broad range of retroviruses in addition to HIV, suggesting that hypermutation by editing is a general innate defence mechanism against this important group of pathogens.