乙型肝炎病毒(HBV)为嗜肝双链DNA病毒,病毒基因组特点如下:①病毒的多聚酶/反转录酶(RT)缺乏校对功能,使HBV较其他DNA病毒更易产生变异;②病毒基因组开放读码框架重叠,1个基因位点上的突变有可能同时引起2种病毒蛋白突变;③生命周期中存在稳定的共价闭合环状DNA(cccDNA);④可以整合到宿主细胞染色体DNA中;⑤病毒蛋白对某些宿主细胞基因表达具有反式调节作用。HBV的这些病毒学特点与乙型肝炎的慢性化和疾病进展密切相关。多位点检测HBVRT基因耐药突变对临床监测病毒耐药、合理进行抗病毒治疗十分重要,分析病毒基因组变异和检测cccDNA对深入了解HBV致病机制与疗效评价有积极意义。技术方法的创新与改进是进行HBV临床病毒学特点研究的基础。
Hepatitis B virus (HBV) is a double-strand hepadnavirus. HBV genomics have unique properties: (1) Viral polymerase/reverse transcriptase (RT) is lackkng in proofreading activity, leading to higher mutation occurrence than other DNA viruses.(2) Overlapping open reading frames in viral genomics may produce the possibility of mutation of two viral proteins mutation as a result of one-site genetic change. (3) A stable covalently closed circular DNA (cccDNA) form exists as an important intermediate in the life cycle. (4) Viral gene fragments may be integrated into host cellular genomic DNA. (5) Viral proteins could be a trans-regulator for certain host cellular protein expression. The virological characteristics of HBV are closely related with the chronicity and disease course of hepatitis B. Multi-site detection of HBV RT-gene mutations is very important for monitoring drug resistance and rational administration of anti-HBV therapy in clinic. Analysis of viral genomic variation and detection of cccDNA are highly valuable in better understanding virological pathogenesis and evaluate therapeutic efficacy. Methodological innovation and improvement is the basis for the study of virological characteristics of HBV.