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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Extensive editing of both hepatitis B virus DNA strands by APOBEC3 cytidine deaminases in vitro and in vivo
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Extensive editing of both hepatitis B virus DNA strands by APOBEC3 cytidine deaminases in vitro and in vivo

机译：APOBEC3胞嘧啶脱氨酶在体内外对乙肝病毒DNA两条链的广泛编辑

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摘要

Because the replication of hepatitis B virus (HBV) proceeds via an obligatory reverse transcription step in the viral capsid, cDNA is potentially vulnerable to editing by cytidine deaminases of the APOBEC3 family. To date only two edited HBV genomes, referred to as G → A hypermutants, have been described in vivo. Recent work suggested that HBV replication was indeed restricted by APOBEC3G but by a mechanism other than editing. The issue of restriction has been explored by using a sensitive PCR method allowing differential amplification of AT-rich DNA. G → A hypermutated HBV genomes were recovered from transfection experiments involving APOBEC3B, -3C, -3F, and -3G indicating that all four enzymes were able to extensively deaminate cytidine residues in minus-strand DNA. Unexpectedly, three of the four enzymes (APOBEC3B, -3F, and -3G) deami-nated HBV plus-strand DNA as well. From the serum of two of four patients with high viremia, G → A hypermutated genomes were recovered at a frequency of ≈10~(-4), indicating that they are, albeit relatively rare, part of the natural cycle of HBV infection. These findings suggest that human APOBEC3 enzymes can impact HBV replication via cytidine deamination.
机译：由于乙型肝炎病毒（HBV）的复制通过病毒衣壳中的强制性逆转录步骤进行，因此cDNA可能容易受到APOBEC3家族胞嘧啶脱氨酶的编辑。迄今为止，在体内仅描述了两个被编辑的HBV基因组，称为G→A超突变体。最近的工作表明，HBOB复制确实受APOBEC3G限制，但受编辑以外的机制限制。通过使用允许富AT DNA差异扩增的灵敏PCR方法，探索了限制的问题。 G→从涉及APOBEC3B，-3C，-3F和-3G的转染实验中回收了超突变的HBV基因组，表明所有四种酶都能够广泛地使负链DNA中的胞苷残基脱氨基。出乎意料的是，四种酶中的三种（APOBEC3B，-3F和-3G）也使HBV正链DNA脱氨基。从4名高病毒血症患者中的2名患者的血清中，以≈10〜（-4）的频率恢复了G→A高突变的基因组，这表明它们虽然很罕见，但却是HBV感染自然周期的一部分。这些发现表明人类APOBEC3酶可通过胞苷脱氨作用影响HBV复制。

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