the g1613a mutation in the hbv genome affects hbeag expression and viral replication through altered core promoter activityg1613a突变在乙肝病毒基因组中影响e抗原表达和病毒复制通过改变核心启动子活动.pdf

The G1613A Mutation in the HBV Genome Affects HBeAg Expression and Viral Replication through Altered Core Promoter Activity 1. 4. 1 1 Man-Shan Li , Terrence Chi-Kong Lau , Sophie Ka-Ping Chan , Chi-Hang Wong , Patrick Kwok-Shing 1 2 2 1,3 Ng , Joseph Jao-Yiu Sung , Henry Lik-Yuen Chan , Stephen Kwok-Wing Tsui * 1 School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China, 2 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China, 3 Centre for Microbial Genomics and Proteomics, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China, 4 Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong SAR, China Abstract Infection of hepatitis B virus (HBV) causes acute and chronic hepatitis and is closely associated with the development of cirrhosis and hepatocellular carcinoma (HCC). Previously, we demonstrated that the G1613A mutation in the HBV negative regulatory element (NRE) is a hotspot mutation in HCC patients. In this study, we further investigated the functional consequences of this mutation in the context of the full length HBV genome and its replication. We showed that the G1613A mutation significantly suppresses the secretion of e antigen (HBeAg) and enhances the synthesis of viral DNA, which is in consistence to our clinical result that the G1613A mutation associates with high viral load in chronic HBV carriers. To further investigate the molecular mechanism of the mutation, we performed the electrop