Evolutionary History and Population Dynamics of Hepatitis E Virus

BackgroundHepatitis E virus (HEV) is an enterically transmitted hepatropic virus. It segregates as four genotypes. All genotypes infect humans while only genotypes 3 and 4 also infect several animal species. It has been suggested that hepatitis E is zoonotic, but no study has analyzed the evolutionary history of HEV. We present here an analysis of the evolutionary history of HEV.
Methods and FindingsThe times to the most recent common ancestors for all four genotypes of HEV were calculated using BEAST to conduct a Bayesian analysis of HEV. The population dynamics for genotypes 1, 3 and 4 were analyzed using skyline plots. Bayesian analysis showed that the most recent common ancestor for modern HEV existed between 536 and 1344 years ago. The progenitor of HEV appears to have given rise to anthropotropic and enzootic forms of HEV, which evolved into genotypes 1 and 2 and genotypes 3 and 4, respectively. Population dynamics suggest that genotypes 1, 3 and 4 experienced a population expansion during the 20th century. Genotype 1 has increased in infected population size ∼30–35 years ago. Genotype 3 and 4 have experienced an increase in population size starting late in the 19th century until ca.1940-45, with genotype 3 having undergone additional rapid expansion until ca.1960. The effective population size for both genotype 3 and 4 rapidly declined to pre-expansion levels starting in ca.1990. Genotype 4 was further examined as Chinese and Japanese sequences, which exhibited different population dynamics, suggesting that this genotype experienced different evolutionary history in these two countries.
ConclusionsHEV appears to have evolved through a series of steps, in which the ancestors of HEV may have adapted to a succession of animal hosts leading to humans. Analysis of the population dynamics of HEV suggests a substantial temporal variation in the rate of transmission among HEV genotypes in different geographic regions late in the 20th Century.

背景：戊型肝炎病毒（Hepatitis E virus, HEV）是一种经消化道传播的嗜肝病毒，可分为四个基因型。所有基因型均可感染人类，而仅基因型3和4还可感染多种动物。有研究提出戊型肝炎为人畜共患病，但目前尚无针对戊型肝炎病毒进化历史的系统分析。本研究开展了戊型肝炎病毒的进化历史分析。

方法与结果：采用BEAST软件对戊型肝炎病毒进行贝叶斯分析，以此推算HEV全部四个基因型的最近共同祖先出现时间。使用天际线图（skyline plots）对基因型1、3、4的种群动态进行分析。贝叶斯分析结果显示，现代HEV的最近共同祖先出现于536至1344年前。戊型肝炎病毒的祖先谱系可分化为嗜人型和兽源性循环型，分别演化形成基因型1、2以及基因型3、4。种群动态分析表明，基因型1、3、4在20世纪均出现了种群扩张：基因型1的感染种群规模在约30至35年前出现显著增长；基因型3和4的种群规模自19世纪晚期开始增长，持续至约1940-1945年，其中基因型3在约1960年前还经历了额外的快速扩张；自约1990年起，基因型3和4的有效种群规模快速回落至扩张前水平。针对基因型4的中日序列亚组分析显示，二者呈现截然不同的种群动态特征，提示该基因型在中、日两国的进化历史存在显著差异。

结论：戊型肝炎病毒的演化过程呈现多阶段性特征，其祖先可能先后适应了一系列动物宿主，最终实现对人类的感染。对戊型肝炎病毒种群动态的分析表明，20世纪晚期，不同地理区域的HEV基因型传播速率存在显著的时间维度差异。