The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA

被引:884
作者
Zhang, H [1 ]
Yang, B [1 ]
Pomerantz, RJ [1 ]
Zhang, CM [1 ]
Arunachalam, SC [1 ]
Gao, L [1 ]
机构
[1] Thomas Jefferson Univ, Dept Med, Div Infect Dis & Environm Med, Ctr Human Virol & Biodef,Dorrance H Hamilton Labs, Philadelphia, PA 19107 USA
关键词
D O I
10.1038/nature01707
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
High mutation frequency during reverse transcription has a principal role in the genetic variation of primate lentiviral populations. It is the main driving force for the generation of drug resistance and the escape from immune surveillance. G to A hypermutation is one of the characteristics of primate lentiviruses, as well as other retroviruses, during replication in vivo and in cell culture(1-6). The molecular mechanisms of this process, however, remain to be clarified. Here, we demonstrate that CEM15 (also known as apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G; APOBEC3G)(7,8), an endogenous inhibitor of human immunodeficiency virus type 1 (HIV-1) replication, is a cytidine deaminase and is able to induce G to A hypermutation in newly synthesized viral DNA. This effect can be counteracted by the HIV-1 virion infectivity factor (Vif). It seems that this viral DNA mutator is a viral defence mechanism in host cells that may induce either lethal hypermutation or instability of the incoming nascent viral reverse transcripts, which could account for the Vif-defective phenotype. Importantly, the accumulation of CEM15-mediated non-lethal hypermutation in the replicating viral genome could potently contribute to the genetic variation of primate lentiviral populations.
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页码:94 / 98
页数:5
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