Mansky L M, Preveral S, Selig L, Benarous R, Benichou S
Department of Molecular Virology, Immunology, and Medical Genetics, Center for Retrovirus Research, and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, Ohio 43210, USA.
J Virol. 2000 Aug;74(15):7039-47. doi: 10.1128/jvi.74.15.7039-7047.2000.
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.
人类免疫缺陷病毒1型（HIV-1）的Vpr蛋白会影响该病毒在体内的突变率。由于Vpr与一种参与DNA修复过程的细胞蛋白——尿嘧啶DNA糖基化酶（UNG）相互作用，我们探究了这种相互作用对HIV-1突变率的影响。对Vpr的单氨基酸变体进行了表征，以确定它们不同的UNG结合特性，并用于反式互补vpr缺失突变型HIV-1。Vpr与UNG相互作用的能力和影响HIV-1突变率的能力之间建立了显著的相关性。我们证明，Vpr掺入病毒颗粒是影响体内突变率和介导UNG核形式的病毒体包装所必需的。UNG被招募到病毒体中表明了Vpr影响逆转录准确性的一种机制。我们的数据表明，灵长类和非灵长类慢病毒进化出了不同的机制来协调尿嘧啶错误掺入慢病毒DNA的问题。
