《生命科学》 2016, 28(3): 344-356

乙型肝炎病毒的变异与进化

童舒平1，2*，王勇翔1，秦艳丽3，叶　雷1，陈朝阳1，宗　莉1，张继明3，闻玉梅1，李纪速2

(1 复旦大学基础医学院病原生物学系/教育部和卫计委医学分子病毒学重点实验室，上海 200032；2 布朗大学医学院暨罗德岛医院肝脏研究中心，罗德岛，美国；3 复旦大学华山医院传染科，上海 200040)

摘　要：摘　要：乙型肝炎病毒(hepatitis B virus， HBV) 是一个很“成功”的病毒，可通过诱导免疫耐受在人群中世代相传。HBV 基因组小而紧凑，不但基因之间重叠，而且编码区与非编码区重叠。如此复杂的基因组如何进化而来尚不清楚，但相关病毒或病毒化石已在鸟类、两栖类、鳄鱼、蛇、乌龟及哺乳类中发现，提示此类病毒存在的历史悠久。全球的HBV 根据序列差异可分成8 种基因型。HBV 慢性感染进程中，机体从免疫耐受期过渡到免疫清除期，导致野生型病毒被突变株替代。首先，介绍HBV 的生命周期；然后，概述病毒的基因型与突变株在慢性感染的建立以及暴发性肝炎与肝癌的发生中所起的作用；最后，通过与相关动物病毒的比较，探讨HBV 可能的进化历程。

Hepatitis B virus: sequence variability and evolution

TONG Shu-Ping1，2*， WANG Yong-Xiang1， QIN Yan-Li3， YE Lei1， CHEN Chao-Yang1，
    ZONG Li1， ZHANG Ji-Ming3， WEN Yu-Mei1， LI Ji-Su2

(1 Department of Pathogen Biology， School of Basic Medical Sciences， Fudan University， Shanghai 200032， China; 2 Liver Research Center， Rhode Island Hospital， Brown University， Providence， Rhode Island， USA; 3 Department of
    Infectious Diseases， Huashan Hospital， Fudan University， Shanghai 200040， China)

Abstract: Abstract: Hepatitis B virus (HBV) is quite successful in vertical transmission in the human host by induction of immune tolerance. It has a tiny but quite compact genome with overlap not only between genes but also between coding and non-coding sequences. How such a complex virus evolved from its more primitive ancestor remains unknown， but the presence of related hepatotropic DNA viruses (hepadnaviruses) or integrated genomic DNA in birds， amphibians， crocodiles， snakes， turtles and mammals suggest an old origin. Today the HBV isolates worldwide can be classified into 8 distinct genotypes. In addition， the transition from immune tolerance phase to the immune clearance phase of chronic infection triggers the replacement of wild-type virus by a series of mutants. This review article will start with an overview of the HBV lifecycle， followed by discussion of the role of viral genotypes and specific mutations on the establishment of chronic infection， development of fulminant hepatitis， or hepatocellular carcinoma. We end by comparing HBV with other members of hepadnaviruses to shed light on its recent evolutionary history.