Dong Qingming, Chan Henry L Y, Liu Zheng, Chan Denise P C, Zhang Bao, Chen Yangchao, Kung Hsiang-Fu, Sung Joseph J Y, He Ming-Liang
Stanley Ho Centre for Emerging Infectious Diseases and Li Ka Shing Institute of Health Sciences, School of Public Health, Prince of Wales Hospital, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
Biochem Biophys Res Commun. 2008 Oct 3;374(4):773-6. doi: 10.1016/j.bbrc.2008.07.115. Epub 2008 Aug 8.
Hepatitis B virus (HBV) infection is a major global health problem that causes over one million deaths annually. A1762T and G1764A mutations in the basal core promoter are often present in HBV patients but seldom in asymptomatic carriers, and are highly correlated with the increased risk of HBV-associated hepatocellular carcinoma (HCC). In this study, for the first time, we show that the basal core promoter activity of HBV strains isolated from asymptomatic carriers is decreased when 1762A is mutated to 1762T or 1764G is mutated to 1764A by site directed mutagenesis. By contrast, the promoter activity of HBV strains isolated from HCC patients is increased when 1762T and 1764A are reversely mutated into 1762A and 1764G, respectively. 1764G contributes more promoter activity than 1762T. We also show that T1762A and G1764A double mutations synergize the reduction of the promoter activity. A mechanism of HBV evasion from host immunoresponse that may facilitate disease development is also discussed.
乙型肝炎病毒（HBV）感染是一个重大的全球健康问题，每年导致超过100万人死亡。HBV患者的基本核心启动子中常常存在A1762T和G1764A突变，而在无症状携带者中则很少见，并且这些突变与HBV相关肝细胞癌（HCC）风险增加高度相关。在本研究中，我们首次通过定点诱变将1762A突变为1762T或1764G突变为1764A后发现，从无症状携带者分离的HBV毒株的基本核心启动子活性降低。相比之下，当1762T和1764A分别反向突变为1762A和1764G时，从HCC患者分离的HBV毒株的启动子活性增加。1764G对启动子活性的贡献大于1762T。我们还表明，T1762A和G1764A双突变协同降低启动子活性。此外，还讨论了一种可能促进疾病发展的HBV逃避宿主免疫反应的机制。
