Luo Kun, Wang Tao, Liu Bindong, Tian Chunjuan, Xiao Zuoxiang, Kappes John, Yu Xiao-Fang
Department of Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
J Virol. 2007 Jul;81(13):7238-48. doi: 10.1128/JVI.02584-06. Epub 2007 Apr 11.
APOBEC3G (A3G) is a single-stranded DNA cytidine deaminase that targets retroviral minus-strand DNA and has potent antiviral activity against diverse retroviruses. However, the mechanisms of A3G antiviral functions are incompletely understood. Here we demonstrate that A3G, A3F, and, to a lesser extent, the noncatalytic A3GC291S block human immunodeficiency virus type 1 (HIV-1) replication by interfering with proviral DNA formation. In HIV-1 virions, A3G interacted with HIV-1 integrase and nucleocapsid, key viral factors for reverse transcription and integration. Unlike A3G, the weak antiviral A3C cytidine deaminase did not interact with either of these factors and did not affect viral reverse transcription or proviral DNA formation. Thus, multiple steps of the HIV-1 replication cycle, most noticeably the formation of proviral DNA, are inhibited by both cytidine deamination-dependent and -independent mechanisms.
载脂蛋白B mRNA编辑酶催化多肽样蛋白3G（A3G）是一种单链DNA胞嘧啶脱氨酶，可靶向逆转录病毒负链DNA，对多种逆转录病毒具有强大的抗病毒活性。然而，A3G抗病毒功能的机制尚未完全明确。在此我们证明，A3G、A3F以及在较小程度上非催化性的A3GC291S通过干扰前病毒DNA的形成来阻断1型人类免疫缺陷病毒（HIV-1）的复制。在HIV-1病毒粒子中，A3G与HIV-1整合酶和核衣壳相互作用，这两者是逆转录和整合的关键病毒因子。与A3G不同，抗病毒能力较弱的A3C胞嘧啶脱氨酶不与上述任何一种因子相互作用，也不影响病毒逆转录或前病毒DNA的形成。因此，HIV-1复制周期的多个步骤，最显著的是前病毒DNA的形成，受到胞嘧啶脱氨依赖性和非依赖性机制的双重抑制。
