Deamination-independent inhibition of hepatitis B virus reverse transcription by APOBEC3G

Deamination-independent inhibition of hepatitis B virus reverse transcription by APOBEC3G
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DOI:
10.1128/jvi.02510-06
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发表时间:
2007-05-01
影响因子:
5.4
通讯作者:
Hu, Jianming
Hu, Jianming
中科院分区:
医学2区
文献类型:
--
作者:
Nguyen, David H.;Gummuluru, Suryaram;Hu, Jianming

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被引文献

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APOBEC3 哺乳动物胞苷脱氨酶家族,包括 APOBEC3G (A3G),已被证明可作为针对逆转录病毒的先天抗病毒因子,并且还可以抑制乙型肝炎病毒 (HBV) 的复制。 A3G 抑制 HBV 复制的机制仍有待阐明。在这项研究中,我们发现APOBEC3蛋白对HBV复制的抑制作用主要在DNA水平,对病毒RNA包装的影响很小。 A3G的抗HBV作用与DNA编辑功能无关,并且抑制模式不是由于HBV DNA降解。 A3G 的独立于编辑的抗病毒活性可以针对 DNA-RNA 杂交体以及单链 DNA。最后,我们表明,与较短的负链 DNA 相比,A3G 优先减少较长负链 DNA 的积累,并表明 A3G 在病毒逆转录过程的早期阶段发挥其抑制作用。
The APOBEC3 family of mammalian cytidine deaminases, including APOBEC3G (A3G), has been shown to function as innate antiviral factors against retroviruses and can also suppress the replication of the hepatitis B virus (HBV). The mechanism by which A3G inhibits HBV replication remains to be elucidated. In this study, we show that the inhibitory effect of APOBEC3 proteins on HBV replication was mainly at the DNA level, with only a minor effect on viral RNA packaging. The anti-HBV effect of A3G was independent of the DNA-editing function, and the mode of inhibition was not due to HBV DNA degradation. The editing-independent antiviral activity of A3G could target DNA-RNA hybrids as well as single-stranded DNA. Finally, we show that there was a preferential decrease in the accumulation of longer minus-strand DNA by A3G, compared to the shorter minus-strand DNA, and suggest that A3G exerts its inhibitory effect at very early stages during viral reverse transcription.