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载脂蛋白B mRNA编辑酶催化多肽样蛋白3G(APOBEC3G)在HIV-1逆转录过程中抑制DNA链转移。

APOBEC3G inhibits DNA strand transfer during HIV-1 reverse transcription.

作者信息

Li Xiao-Yu, Guo Fei, Zhang Li, Kleiman Lawrence, Cen Shan

机构信息

Lady Davis Institute for Medical Research and McGill AIDS Centre, Jewish General Hospital, Department of Medicine, McGill University, Montreal, Quebec H3T 1E2, Canada.

出版信息

J Biol Chem. 2007 Nov 2;282(44):32065-74. doi: 10.1074/jbc.M703423200. Epub 2007 Sep 12.

Abstract

Human APOBEC3G (hA3G) has been identified as an anti-HIV-1 host factor. The presence of hA3G in HIV-1 strongly inhibits the ability of the virus to produce new viral DNA upon infection. In this report, we demonstrate that the reduction of late viral DNA synthesis is due to the inhibition by hA3G of the strand transfer steps that occur during reverse transcription. Analysis of viral cDNA intermediates in vivo reveals that hA3G causes an inhibition of the minus and plus strand transfers, without having a significant impact on DNA elongation. Using an in vitro system to measure minus strand transfer similarly shows a dose-dependent reduction of strand transfer by hA3G. This inhibition of strand transfer occurs independently the editing activity of hA3G and is correlated with its ability to prevent RNaseH degradation of the template RNA.

摘要

人类载脂蛋白B mRNA编辑酶催化多肽样蛋白3G(hA3G)已被鉴定为一种抗HIV-1的宿主因子。HIV-1中hA3G的存在强烈抑制病毒在感染后产生新病毒DNA的能力。在本报告中,我们证明晚期病毒DNA合成的减少是由于hA3G对逆转录过程中发生的链转移步骤的抑制。体内病毒cDNA中间体的分析表明,hA3G会抑制负链和正链转移,而对DNA延伸没有显著影响。使用体外系统测量负链转移同样显示hA3G对链转移有剂量依赖性的降低。这种对链转移的抑制独立于hA3G的编辑活性,并且与其防止模板RNA被核糖核酸酶H降解的能力相关。

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