Genetic editing of HBV DNA by monodomain human APOBEC3 cytidine deaminases and the recombinant nature of APOBEC3G.
Genetic editing of HBV DNA by monodomain human APOBEC3 cytidine deaminases and the recombinant nature of APOBEC3G.
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DOI：
10.1371/journal.pone.0004277
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Vartanian JP
中科院分区：
文献类型：
--
作者：
Henry M;Guétard D;Suspène R;Rusniok C;Wain-Hobson S;Vartanian JP
B型肝炎病毒（HBV）DNA易受APOBEC 3（A3 A-H）家族的人胞苷脱氨酶的编辑，尽管其水平比HIV cDNA低得多。我们分析和比较了鹌鹑细胞系中所有七种酶的HBV编辑，该细胞系不产生任何内源性DNA胞苷脱氨酶活性。使用3DPCR，可以显示除了A3 DE之外的所有人都能够在体外以10−2至10−5的水平对HBV DNA进行脱氨基，其中A3 A被证明是最有效的编辑器。单独的A3 G氨基末端结构域完全没有脱氨酶活性，在3DPCR的灵敏度范围内（Δ 10−4至Δ 10−5）。对二核苷酸编辑背景的详细分析表明，只有A3 G和A3 H具有强烈的偏好，特别是CpC和TpC。A3外显子的同源性分析表明，A3 G实际上是一个嵌合体，前两个外显子来自A3 F基因。这可能允许能够有效限制HIV-1Δvif的两个基因的共表达。
Hepatitis B virus (HBV) DNA is vulnerable to editing by human cytidine deaminases of the APOBEC3 (A3A-H) family albeit to much lower levels than HIV cDNA. We have analyzed and compared HBV editing by all seven enzymes in a quail cell line that does not produce any endogenous DNA cytidine deaminase activity. Using 3DPCR it was possible to show that all but A3DE were able to deaminate HBV DNA at levels from 10−2 to 10−5 in vitro, with A3A proving to be the most efficient editor. The amino terminal domain of A3G alone was completely devoid of deaminase activity to within the sensitivity of 3DPCR (∼10−4 to 10−5). Detailed analysis of the dinucleotide editing context showed that only A3G and A3H have strong preferences, notably CpC and TpC. A phylogenic analysis of A3 exons revealed that A3G is in fact a chimera with the first two exons being derived from the A3F gene. This might allow co-expression of the two genes that are able to restrict HIV-1Δvif efficiently.
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