Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA.
Nat Immunol. 2011 Aug 28;12(10):975-83. doi: 10.1038/ni.2087.
APOBEC3G (A3G) is an intrinsic antiviral factor that inhibits the replication of human immunodeficiency virus (HIV) by deaminating cytidine residues to uridine. This causes guanosine-to-adenosine hypermutation in the opposite strand and results in inactivation of the virus. HIV counteracts A3G through the activity of viral infectivity factor (Vif), which promotes degradation of A3G. We report that viral protein R (Vpr), which interacts with a uracil glycosylase, also counteracted A3G by diminishing the incorporation of uridine. However, this process resulted in activation of the DNA-damage-response pathway and the expression of natural killer (NK) cell-activating ligands. Our results show that pathogen-induced deamination of cytidine and the DNA-damage response to virus-mediated repair of the incorporation of uridine enhance the recognition of HIV-infected cells by NK cells.
APOBEC3G（A3G）是一种内在的抗病毒因子，通过脱氨酶将胞嘧啶残基转化为尿嘧啶来抑制人类免疫缺陷病毒（HIV）的复制。这会导致互补链中的鸟嘌呤-腺嘌呤超突变，从而使病毒失活。HIV 通过病毒感染力因子（Vif）的活性来对抗 A3G，Vif 促进 A3G 的降解。我们报告称，与尿嘧啶糖苷酶相互作用的病毒蛋白 R（Vpr）也通过减少尿嘧啶的掺入来对抗 A3G。然而，这一过程激活了 DNA 损伤反应途径，并表达了自然杀伤（NK）细胞激活配体。我们的结果表明，病原体诱导的胞嘧啶脱氨酶和病毒介导的尿嘧啶掺入修复的 DNA 损伤反应增强了 NK 细胞对 HIV 感染细胞的识别。
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