Dual effect of APOBEC3G on Hepatitis B virus
Dual effect of APOBEC3G on Hepatitis B virus
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DOI：
10.1099/vir.0.82319-0
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发表时间：
2007-02-01
影响因子：
3.8
通讯作者：
Chayama, Kazuaki
中科院分区：
文献类型：
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作者：
Noguchi, Chiemi;Hiraga, Nobuhiko;Chayama, Kazuaki
B型肝炎病毒（HBV）和逆转录病毒的G至A超突变是宿主APOBEC蛋白脱氨基活性的结果，并且被认为在先天性抗病毒免疫中起作用。据报道，α和γ干扰素（IFN-α和IFN-γ）可上调APOBEC 3G的转录，已知APOBEC 3G可减少HBV的复制。我们通过开发定量测量来研究在各种条件下高度突变的基因组的数量。在HepG 2细胞系中，高度突变的HBV水平为2.3/10（4）个HBV基因组，但在允许的Huh 7细胞中仅为0.5/10（4）个。HepG 2细胞中APOBEC 3G mRNA的水平比Huh 7细胞高约10倍。用IFN-α或IFN-γ处理HepG 2细胞增加了APOBEC 3G的转录和HBV的超突变。IFN-γ比IFN-α更显著地诱导这些mRNA和HBV基因组的超突变。两种干扰素都能减少乙型肝炎病毒复制中间体的数量。APOBEC 3G的过表达减少了HBV复制中间体的数量，并使高度突变的基因组增加了334倍，在104个基因组中达到968个。脱氨失活的APOBEC 3G不诱导超突变，但同样减少了病毒。我们的研究结果表明，APOBEC 3G，IFN上调，对HBV有双重作用：诱导超突变和减少病毒的合成。超突变对感染性的影响有待进一步研究。
G to A hypermutation of Hepatitis B virus (HBV) and retroviruses appears as a result of deamination activities of host APOBEC proteins and is thought to play a role in innate antiviral immunity. Alpha and gamma interferons (IFN-alpha and -gamma) have been reported to upregulate the transcription of APOBEC3G, which is known to reduce the replication of HBV. We investigated the number of hypermutated genomes under various conditions by developing a quantitative measurement. The level of hypermutated HBV in a HepG2 cell line, which is semi-permissive for retrovirus, was 2.3 in 10(4) HBV genomes, but only 0.5 in 10(4) in permissive Huh7 cells. The level of APOBEC3G mRNA was about ten times greater in HepG2 cells than in Huh7 cells. Treatment of HepG2 cells with either IFN-alpha or -gamma increased the transcription of APOBEC3G and hypermutation of HBV. These mRNAs and hypermutation of HBV genomes were induced more prominently by IFN-gamma than by IFN-alpha. Both IFNs decreased the number of replicative intermediate of HBV. Overexpression of APOBEC3G reduced the number of replicative intermediate of HBV and increased hypermutated genomes 334 times, reaching 968 in 104 genomes. Deamination-inactive APOBEC3G did not induce hypermutation, but reduced the virus equally. Our results suggest that APOBEC3G, upregulated by IFNs, has a dual effect on HBV: induction of hypermutation and reduction of virus synthesis. The effect of hypermutation on infectivity should be investigated further.