Bonvin Marianne, Greeve Jobst
Department of Clinical Research, Switzerland, University of Berne, Berne, Switzerland.
Curr Opin Infect Dis. 2008 Jun;21(3):298-303. doi: 10.1097/QCO.0b013e3282fe1bb2.
APOBEC3 editing enzymes inhibit retroviruses by cytidine deamination in minus-strand cDNA, leading to G to A hypermutated proviruses, and by less well characterized inhibition of retroviral replication independently of catalysis. This review focuses on the effects of APOBEC3 enzymes on the pararetrovirus hepatitis B virus.
The cytidine deaminases APOBEC3B, APOBEC3C, APOBEC3F and APOBEC3G deaminate cytidine residues in hepatitis-B-virus minus-strand cDNA, resulting in G to A hypermutated genomes in the serum of hepatitis-B-virus-infected patients. APOBEC3B, APOBEC3F and APOBEC3G directly inhibit hepatitis-B-virus reverse transcription independently of deaminase activity. In human liver, APOBEC3B, APOBEC3F and APOBEC3G are expressed to low levels, but in human primary hepatocytes stimulated with interferon-alpha, APOBEC3G is induced to levels sufficient for hepatitis-B-virus inhibition. APOBEC3B inhibits hepatitis-B-virus gene transcription, and APOBEC3B and APOBEC3G preferentially mutate the hepatitis-B-virus x gene leading to the truncated hepatitis-B-virus x variants in hepatitis-B-virus-associated liver cancer.
The interferon-inducible APOBEC3G and the other APOBEC3s restrict hepatitis B virus by cytidine deamination in hepatitis-B-virus minus-strand cDNA and by direct inhibition of hepatitis-B-virus reverse transcriptase. The nuclear localized APOBEC3B is implicated in liver cancer development. To what extent these enzymes contribute to noncytolytic clearance of hepatitis B virus in vivo remains to be defined, yet the APOBEC3 cytidine deaminases are likely to play a role in these processes.
载脂蛋白B mRNA编辑酶3（APOBEC3）编辑酶通过在负链cDNA中进行胞嘧啶脱氨作用抑制逆转录病毒，导致前病毒发生G到A的超突变，并且通过尚未完全明确的独立于催化作用的机制抑制逆转录病毒复制。本综述聚焦于APOBEC3酶对副逆转录病毒乙型肝炎病毒的影响。
胞嘧啶脱氨酶APOBEC3B、APOBEC3C、APOBEC3F和APOBEC3G使乙型肝炎病毒负链cDNA中的胞嘧啶残基脱氨，导致乙型肝炎病毒感染患者血清中的基因组发生G到A的超突变。APOBEC3B、APOBEC3F和APOBEC3G独立于脱氨酶活性直接抑制乙型肝炎病毒逆转录。在人肝脏中，APOBEC3B、APOBEC3F和APOBEC3G表达水平较低，但在α干扰素刺激的人原代肝细胞中，APOBEC3G被诱导至足以抑制乙型肝炎病毒的水平。APOBEC3B抑制乙型肝炎病毒基因转录，并且APOBEC3B和APOBEC3G优先使乙型肝炎病毒X基因发生突变，导致乙型肝炎病毒相关肝癌中出现截短的乙型肝炎病毒X变异体。
干扰素诱导的APOBEC3G和其他APOBEC3通过乙型肝炎病毒负链cDNA中的胞嘧啶脱氨作用以及直接抑制乙型肝炎病毒逆转录酶来限制乙型肝炎病毒。定位于细胞核的APOBEC3B与肝癌发展有关。这些酶在体内对乙型肝炎病毒非细胞溶解性清除的贡献程度尚待确定，但APOBEC3胞嘧啶脱氨酶很可能在这些过程中发挥作用。
