Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome
Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome
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DOI：
10.1038/nsmb758
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发表时间：
2004-05-01
影响因子：
16.8
通讯作者：
Landau, NR
中科院分区：
文献类型：
--
作者：
Yu, Q;König, R;Landau, NR
HIV-1缺失的vif辅助基因封装了细胞胞苷脱氨酶APOBEC3G。感染后，封装的APOBEC3G在病毒逆转录物中诱导G A突变。G- >A突变是由负链的C- >U脱氨或两条链的脱氨后再修复正链引起的。我们在这里报道，负链脱胺作用发生在病毒基因组的长度上，优先发生在CCCA序列上，频率在5‘- >3’方向上渐变。APOBEC3G在5' U3和引物结合位点诱导了以前未检测到的C T突变，这两个位点在反转录过程中都变成了短暂的单链。在体外，APOBEC3G结合和脱氨单链DNA (ssDNA)，但不结合双链DNA （dsDNA）或DNA- rna杂交体。我们提出，对ssDNA的需求解释了负链突变，5‘- > - 3’分级脱氨频率和罕见的C - T突变。
HIV-1 deleted for the vif accessory gene encapsidates the cellular cytidine deaminase APOBEC3G. Upon infection, the encapsidated APOBEC3G induces G A mutations in the viral reverse transcripts. The G-->A mutations result either from C-->U deamination of the minus strand or deamination of both strands followed by repair of the plus strand. We report here that minus-strand deamination occurred over the length of the virus genome, preferentially at CCCA sequences, with a graded frequency in the 5'-->3' direction. APOBEC3G induced previously undetected C T mutations in the 5' U3 and the primer-binding site, both of which become transiently single-stranded during reverse transcription. In vitro, APOBEC3G bound and deaminated single-stranded DNA (ssDNA) but not double-stranded DNA (dsDNA) or DNA-RNA hybrids. We propose that the requirement for ssDNA accounts for the minus-strand mutations, the 5'-->3' graded frequency of deamination and the rare C T mutations.