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乙型肝炎e抗原阴性的暴发性乙型肝炎患者中乙型肝炎病毒前核心区的基因突变及前核心变异体的体外翻译

Genetic mutations of precore region of hepatitis B virus in hepatitis B e antigen-negative patients with fulminant hepatitis B and translation of precore variants in vitro.

作者信息

Guo Y, Hou J, Luo K, Feng X

机构信息

Department of Infectious Disease, Nanfang Hospital, First Military Medical University, Guangzhou 510515, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2001 Feb;9(1):42-4.

PMID:11242136
Abstract

OBJECTIVE

To detect mutations in precore region of hepatitis B virus of HBeAg negative- patients with fulminant hepatitis and to determine the effect of T1862 mutants on synthesis of precursor of hepatitis B e antigen.

METHODS

The entire precore and core region were amplified from sera of nine HBeAg negative-patients with fulminant hepatitis B by polymerase chain reaction (PCR). PCR products were cloned into plasmid pUC18, and sequencing for analysis of precore mutations. Precore and core sequence of T1862 variant were also cloned into expression plasmid pGEMT for in vitro transcription and translation study on synthesis and procession of e antigen.

RESULTS

Three variants, A1896, A1899 and T1862, whose nucleotide mutation led to amino acids substitutions, were detected in patients with fulminant hepatitis. T1862 variant didn't effect the synthesis of precursor of e antigen. Also there was no variant detected in precore region of hepatitis B virus in two patients.

CONCLUSIONS

The causes for negative of e antigen in fulminant hepatitis patients may be partially explained by precore mutation of A1896 and T1862, and the latter variant may effect the process of precursor of e antigen, rather than the synthesis of precursor protein.

摘要

目的

检测暴发性肝炎HBeAg阴性患者乙肝病毒前核心区的突变情况,并确定T1862突变体对乙肝e抗原前体合成的影响。

方法

采用聚合酶链反应(PCR)从9例暴发性乙型肝炎HBeAg阴性患者的血清中扩增整个前核心区和核心区。将PCR产物克隆到质粒pUC18中,进行测序以分析前核心区突变。T1862变异体的前核心区和核心区序列也被克隆到表达质粒pGEMT中,用于对e抗原的合成和加工进行体外转录和翻译研究。

结果

在暴发性肝炎患者中检测到3种变异体,即A1896、A1899和T1862,其核苷酸突变导致氨基酸替换。T1862变异体不影响e抗原前体的合成。另外,在2例患者的乙肝病毒前核心区未检测到变异体。

结论

暴发性肝炎患者e抗原阴性的原因可能部分由A1896和T1862的前核心区突变所解释,后一种变异体可能影响e抗原前体加工过程,而非前体蛋白的合成。

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