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

Article

关键词: HUMAN-IMMUNODEFICIENCY-VIRUS;    B MESSENGER-RNA;    TYPE-1 VIF PROTEIN;    REVERSE TRANSCRIPTION;    G->A HYPERMUTATION;    NONPERMISSIVE CELLS;    EDITING ENZYME;    SOR GENE;    INFECTION;    REPLICATION;   

DOI  :  10.1038/nature01707

来源: SCIE

【 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.

【 授权许可】

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