小分子乙型肝炎病毒基因组缺失突变体结构分析  

Structural analysis of small deletion mutants of hepatitis B virus

作　　者：郭丹华[1] 王林[1] 黄清玲[1] 林万松[1] 陈婉南[1] 林旭[1] 

机构地区：[1]福建医科大学分子医学研究中心,福建省高校感染与肿瘤重点实验室,福州350004

出　　处：《中华传染病杂志》2008年第3期132-137,共6页Chinese Journal of Infectious Diseases

基　　金：全国优秀博士学位论文作者专项资金资助项目（200359）;福建省重大科技基金项目（2002F005）;福建省高等学校科技创新团队培育计划基金项目（FMU-RT00]）

摘　　要：目的 了解小分子HBV基因组缺失突变体的基因结构及特点。方法 采用一步法PCR从慢性乙型肝炎患者血清中扩增全基因组HBVDNA，回收并克隆〈1kb的小分子HBVDNA，测序并以BioEdit及VectorNTI6．0软件分析基因结构特点。结果获得基因长度介于174～986bp之间的64种、共124个小分子HBV缺失突变体DNA，按基因结构特点分为3类，即3种GT-AG剪接变异体、29种“常规”缺失突变体及32种基因组内部含polyA的缺失突变体。所有小分子基因组缺失突变体在HBV各编码区及基因调控区均存在不同程度缺失，其中66％（42／64种）保留与HBV复制（包装）相关的所有顺式调控序列，48％（31／64种）保留X编码区。结论 乙型肝炎患者血清中普遍存在小分子HBV基因组缺失突变体，深入了解这些变异体的结构和功能，有助于进一步探索HBV的致病机制。Objective To elucidate the genome organization of small deletion mutants of hepatitis B virus （HBV）. Methods Amplified the HBV genomes by polymerase chain reaction from the serum of the patients with chronic hepatitis B and cloned the small HBV DNA less than 1 kb, then sequenced and analyzed the gene organization of these small deletion mutants of HBV. Results Totally one hundred and twenty-four small deletion mutants of HBV genomes categorized to sixty-four types were obtained and classified into three groups according to the criteria of the characteristics of gene organization, for example, spliced variants, regular deletion mutants and the deletion mutants with an internal poly （dA）. All of these isolated mutants shared some common features as the deletion in coding regions and regulatory elements, 66% of the mutants retained the cis elements crucial for the viral replication and encapsidation, while 48% retained the X region. Conclusions Small deletion mutants of HBV are commonly detected in the serum from chronic hepatitis B patients, the characteristic structure of such mutants implies that they might be closely co-related with the pathogenicity of HBV. The exact mechanisms need further study yet.

关 键 词：肝炎病毒 乙型 基因缺失 基因组 突变 聚合酶链反应 

分 类 号：R512.62[医药卫生—内科学] R392-33[医药卫生—临床医学]