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

乙型肝炎病毒增强子2/核心启动子突变分析及其在乙型肝炎中的功能作用

基本信息

批准号：
06670521
负责人：
YOKOSUKA Osamu
金额：
$ 1.34万
依托单位：
CHIBA UNIBERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670521/
关键词：
Hepatitis B virus HBV-DNA Enhancer 2 Core promoter CAT actiity B型肝炎ウイルス HBV‐DNA コアプロモーター

项目摘要

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.

B型肝炎病毒引起肝脏疾病的机制尚不清楚。有研究表明，B型肝炎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/核心启动子区被认为与核心肽的表达密切相关。我们检测了这些区域中可能与B型肝炎相关的突变。通过对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例无症状携带者有11个核苷酸突变（1.2个/例），17例慢性肝炎患者有73个核苷酸突变（4.3个/例），4例急性肝炎有4个核苷酸突变（1.0个/例），4例暴发性肝炎有11个核苷酸突变，6例致死性急性加重期有25个核苷酸突变。最频繁的替换在nt处被识别。1764年，在1766.增强子2/核心启动子区的突变被认为是核心启动子功能的重要位点。突变前后增强子活性无明显差异，提示增强子2/核心启动子区的突变可能影响前核心信息的表达，从而影响B型肝炎的发病机制。