Okada Ayaka, Iwatani Yasumasa
Department of Microbiology and Immunology, Laboratory of Infectious Diseases, Clinical Research Center, National Hospital Organization Nagoya Medical Center Nagoya, Japan.
Department of Microbiology and Immunology, Laboratory of Infectious Diseases, Clinical Research Center, National Hospital Organization Nagoya Medical CenterNagoya, Japan; Department of AIDS Research, Nagoya University Graduate School of MedicineNagoya, Japan.
Front Microbiol. 2016 Dec 19;7:2027. doi: 10.3389/fmicb.2016.02027. eCollection 2016.
APOBEC3G (A3G) is a member of the cellular polynucleotide cytidine deaminases, which catalyze the deamination of cytosine (dC) to uracil (dU) in single-stranded DNA. These enzymes potently inhibit the replication of a variety of retroviruses and retrotransposons, including HIV-1. A3G is incorporated into -deficient HIV-1 virions and targets viral reverse transcripts, particularly minus-stranded DNA products, in newly infected cells. It is well established that the enzymatic activity of A3G is closely correlated with the potential to greatly inhibit HIV-1 replication in the absence of Vif. However, the details of the underlying molecular mechanisms are not fully understood. One potential mechanism of A3G antiviral activity is that the A3G-dependent deamination may trigger degradation of the dU-containing reverse transcripts by cellular uracil DNA glycosylases (UDGs). More recently, another mechanism has been suggested, in which the virion-incorporated A3G generates lethal levels of the G-to-A hypermutation in the viral DNA genome, thus potentially driving the viruses into "error catastrophe" mode. In this mini review article, we summarize the deaminase-dependent and deaminase-independent molecular mechanisms of A3G and discuss how A3G-mediated deamination is linked to antiviral mechanisms.
载脂蛋白B mRNA编辑酶催化多肽样蛋白3G（APOBEC3G，A3G）是细胞多核苷酸胞嘧啶脱氨酶家族的成员，可催化单链DNA中的胞嘧啶（dC）脱氨生成尿嘧啶（dU）。这些酶可有效抑制多种逆转录病毒和逆转座子的复制，包括HIV-1。A3G被整合到缺乏Vif的HIV-1病毒颗粒中，并在新感染的细胞中靶向病毒逆转录产物，特别是负链DNA产物。众所周知，在没有Vif的情况下，A3G的酶活性与极大抑制HIV-1复制的潜力密切相关。然而，其潜在分子机制的细节尚未完全了解。A3G抗病毒活性的一种潜在机制是，A3G依赖的脱氨作用可能会触发细胞尿嘧啶DNA糖基化酶（UDG）对含dU逆转录产物的降解。最近，又提出了另一种机制，即病毒颗粒中整合的A3G会在病毒DNA基因组中产生致死水平的G到A超突变，从而可能使病毒进入“错误灾难”模式。在这篇小型综述文章中，我们总结了A3G依赖脱氨酶和不依赖脱氨酶的分子机制，并讨论了A3G介导的脱氨作用如何与抗病毒机制相关联。
