The interaction of Vpr with uracil DNA glycosylase modulates the human immunodeficiency virus type 1 in vivo mutation rate
The interaction of Vpr with uracil DNA glycosylase modulates the human immunodeficiency virus type 1 in vivo mutation rate
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DOI：
10.1128/jvi.74.15.7039-7047.2000
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发表时间：
2000-08-01
影响因子：
5.4
通讯作者：
Benichou, S
中科院分区：
文献类型：
--
作者：
Mansky, LM;Preveral, S;Benichou, S
人类免疫缺陷病毒1型（HIV-1）的Vpr蛋白影响病毒的体内突变率。由于Vpr与DNA修复过程中涉及的细胞蛋白尿嘧啶DNA糖基化酶（UNG）相互作用，我们探讨了这种相互作用对HIV-1突变率的贡献。Vpr的单氨基酸变体的特征在于其差异UNG结合特性，并用于反式互补vpr无效突变体HIV-1。Vpr与UNG相互作用的能力和影响HIV-1突变率的能力之间存在显著的相关性。我们证明，Vpr掺入到病毒颗粒中需要影响体内突变率和介导病毒粒子包装的核形式的UNG。UNG向病毒粒子中的募集表明Vpr如何影响逆转录准确性的机制。我们的数据表明，在灵长类和非灵长类慢病毒中进化出不同的机制来调和尿嘧啶错误掺入慢病毒DNA。
The Vpr protein of human immunodeficiency virus type 1 (HIV-1) influences the in vivo mutation rate of the virus. Since Vpr interacts with a cellular protein implicated in the DNA repair process, uracil DNA glycosylase (UNG), we have explored the contribution of this interaction to the mutation rate of HIV-1. Single-amino-acid variants of Vpr were characterized for their differential UNG-binding properties and used to trans complement vpr null mutant HIV-1. A striking correlation was established between the abilities of Vpr to interact with UNG and to influence the HIV-1 mutation rate. We demonstrate that Vpr incorporation into virus particles is required to influence the in vivo mutation rate and to mediate virion packaging of the nuclear form of UNG. The recruitment of UNG into virions indicates a mechanism for how Vpr can influence reverse transcription accuracy. Our data suggest that distinct mechanisms evolved in primate and nonprimate lentiviruses to reconcile uracil misincorporation into lentiviral DNA.