Blum H E
Department of Internal Medicine, University of Zürich, Switzerland.
Intervirology. 1993;35(1-4):40-50. doi: 10.1159/000150294.
Mutations of viral genomes are normal biological events and result in the coexistence of viral genotypes in infected individuals ('quasispecies'). Hepatitis B virus (HBV) and the related animal hepadnaviruses have a mutation rate which is intermediate between DNA and RNA viruses because they replicate asymmetrically via reverse transcription of an RNA intermediate. HBV mutants affecting all known reading frames of the viral genome have been demonstrated in patients with acute fulminant or chronic HBV infection. Some of the mutations identified to date suggest a contribution to viral latency, low level HBV infection, the severity of liver disease and vaccine escape. Since most viral genomes carry more than one mutation and most individuals are infected by more than one variant, the demonstration of a causal relationship between a single mutation and a biological or pathobiological effect requires the in vitro and in vivo analysis of genetically defined mutants. Such analyses should allow a molecular understanding of the genetic contribution of HBV to the variable natural course of HBV infection, ranging from an asymptomatic healthy carrier state to acute or even fulminant hepatitis, chronic liver disease, liver cirrhosis and hepatocellular carcinoma.
病毒基因组的突变是正常的生物学事件，会导致感染个体中病毒基因型的共存（“准种”）。乙型肝炎病毒（HBV）及相关的动物嗜肝DNA病毒的突变率介于DNA病毒和RNA病毒之间，因为它们通过RNA中间体的逆转录进行不对称复制。在急性暴发性或慢性HBV感染患者中已证实存在影响病毒基因组所有已知阅读框的HBV突变体。迄今为止鉴定出的一些突变表明其与病毒潜伏、低水平HBV感染、肝病严重程度及疫苗逃逸有关。由于大多数病毒基因组携带不止一个突变，且大多数个体感染的不止一种变体，因此要证明单个突变与生物学或病理生物学效应之间的因果关系，需要对基因明确的突变体进行体外和体内分析。此类分析应有助于从分子层面理解HBV对HBV感染自然病程多变性的遗传贡献，HBV感染的自然病程范围从无症状健康携带者状态到急性甚至暴发性肝炎、慢性肝病、肝硬化和肝细胞癌。
