ANALYSIS OF MUTATIONS IN HEPATITIS B VIRUS ENHANCER 2/CORE PROMOTER ANT THEIR FUNCTIONAL ROLES IN HEPATITIS B

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The mechanism of liver diseases by hepatitis B virus is still unknown. Several studies have suggested that the hepatitis B core antigen peptides could be the immunological targets of cytotoxic T lymphocytes. Enhancer 2/ core promoter regions are thougth to have close relationship to the expression of the core peptides. We examined the mutations in these regions which may be related to type B hapatitis. The entire nucleotide sequence from enhancer 2/ core promoter regions were investigated by direct sequencing of the amplified products derived from 40 patients with HBV infection. In enhancer 2/ core promoter region, there were 11 nucleotide mutations in 9 asymptomatic carriers (1.2/case) and 73 in 17 chronic hepatitis patients (4.3/case) , 4 mutations in 4 acute hepatitis (1.0/case) , 11 in 4 fulminant hepatitis, 25 in 6 fatal acute exacerbations. The most frequent substitutions were recognized at nt. 1764 and at nt. 1766. Thses mutation in enhancer 2/core promoter region were considered to be an important site fore core promoter function. There was no difference in enhancer activity between the sequences with or without mutation.These data suggest that mutations in the enhancer 2/core promoter region could affect the expression of the precore message and might have influence in the pathogenesis of type B hepatitis.