Department of Molecular Genetics, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
Biochem Biophys Res Commun. 2019 Oct 8;518(1):26-31. doi: 10.1016/j.bbrc.2019.08.003. Epub 2019 Aug 7.
Some APOBEC3 family members have antiviral activity against retroviruses and DNA viruses. Hepatitis B virus (HBV) is a DNA virus that is the major causative factor of severe liver diseases such as cirrhosis and hepatocellular carcinoma. To determine whether APOBEC3 variants in humans have different anti-HBV activities, we evaluated natural variants of APOBEC3C, APOBEC3G, and APOBEC3H using an HBV-replicating cell culture model. Our data demonstrate that the APOBEC3C variant S188I had increased restriction activity and hypermutation frequency against HBV DNA. In contrast, the APOBEC3G variant H186R did not alter the anti-HBV and hypermutation activities. Among APOBEC3H polymorphisms (hap I-VII) and splicing variants (SV-200, SV-183, SV-182, and SV-154), hap II SV-183 showed the strongest restriction activity. These data suggest that the genetic variations in APOBEC3 genes may affect the efficiency of HBV elimination in humans.
一些 APOBEC3 家族成员具有抗逆转录病毒和 DNA 病毒的活性。乙型肝炎病毒（HBV）是一种 DNA 病毒，是肝硬化和肝细胞癌等严重肝脏疾病的主要致病因素。为了确定人类的 APOBEC3 变体是否具有不同的抗 HBV 活性，我们使用 HBV 复制细胞培养模型评估了 APOBEC3C、APOBEC3G 和 APOBEC3H 的天然变体。我们的数据表明，APOBEC3C 变体 S188I 对 HBV DNA 的限制活性和高频突变频率增加。相比之下，APOBEC3G 变体 H186R 并未改变抗 HBV 和高频突变活性。在 APOBEC3H 多态性（hap I-VII）和剪接变体（SV-200、SV-183、SV-182 和 SV-154）中，hap II SV-183 显示出最强的限制活性。这些数据表明，APOBEC3 基因的遗传变异可能影响人类 HBV 清除的效率。
