title: A1762T/G1764A mutations of hepatitis B virus, associated with the increased risk of hepatocellular carcinoma, reduce basal core promoter activities.
abstract: 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.
authors.affiliation: 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.
authors.forename: Qingming
authors.initials: Q
authors.lastname: Dong
authors.forename: Henry L Y
authors.initials: HL
authors.lastname: Chan
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Denise P C
authors.initials: DP
authors.lastname: Chan
authors.forename: Bao
authors.initials: B
authors.lastname: Zhang
authors.forename: Yangchao
authors.initials: Y
authors.lastname: Chen
authors.forename: Hsiang-Fu
authors.initials: HF
authors.lastname: Kung
authors.forename: Joseph J Y
authors.initials: JJ
authors.lastname: Sung
authors.forename: Ming-Liang
authors.initials: ML
authors.lastname: He
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D005838:Genotype; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D012306:Risk; D014758:Viral Core Proteins / Q000235:genetics*
chemical_list: D014758:Viral Core Proteins