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

乙型肝炎病毒引起肝脏疾病的机制尚不清楚。一些研究表明乙肝核心抗原肽可能是细胞毒性T淋巴细胞的免疫靶点。增强子2/核心启动子区域被认为与核心肽的表达密切相关。我们检查了这些可能与B型肝炎有关的区域的突变。通过对来自40例HBV感染患者的扩增产物进行直接测序，研究了增强子2/核心启动子区域的整个核苷酸序列。在增强子2/核心启动子区，9例无症状携带者中有11个核苷酸突变（1.2/例），17例慢性肝炎患者中有73个核苷酸突变（4.3/例），4例急性肝炎患者中有4个核苷酸突变（1.0/例），4例暴发性肝炎患者中有11个核苷酸突变，6例致死性急性加重患者中有25个核苷酸突变。在nt. 1764和nt. 1766被确认为最常见的替换。增强子2/核心启动子区域的突变被认为是核心启动子功能的重要位点。增强子活性在有或没有突变的序列之间没有差异。这些数据表明增强子2/核心启动子区域的突变可能影响前前信息的表达，并可能影响乙型肝炎的发病机制。

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.