目标:甲型肝炎病毒(HAV),主要通过粪便-口腔途径传播,是世界范围内急性病毒性肝炎的主要病因之一。HAV在中国是地方病。这项研究对在该国传播的HAV分离株进行了遗传和进化分析。
方法:收集临床样本并分析HAV核苷酸和推导的氨基酸序列。使用贝叶斯马尔可夫链蒙特卡罗方法(BEAST软件,版本1.7.5)。
结果:本研究中来自中国的所有分离株均属于I型,大多数样本聚集在亚基因型IA中,同时观察到几种独特的氨基酸变体。估计平均替代率为5.56×10(-4)个替代/站点/年,据计算,到中国基因型I分离株的最新共同祖先的时间约为180年前。天际线地块显示,从1990年代中期开始,HAV的发病率逐渐下降。
结论:进化估计与实验室和流行病学结果一致。来自中国的几个分离株显示接近免疫显性位点的氨基酸变化,这需要进一步分析。研究结果表明,在中国,提高经济和卫生水平以及接种HAV疫苗以控制HAV相关感染的有效性。
OBJECTIVE: Hepatitis A virus (HAV), transmitted mainly through the fecal-oral route, is one of the major causes of acute viral hepatitis worldwide. HAV is endemic in
China. This study performed genetic and evolutionary analysis of HAV isolates circulated in the country.
METHODS: Clinical samples were collected and HAV nucleotide and deduced amino acid sequences were analyzed. 70 representative sequences of HAV VP3-VP1-2A regions sampled from 1988 to 2014 were compared and characterized using the Bayesian Markov Chain Monte Carlo approach (BEAST software, Version1.7.5).
RESULTS: All isolates from
China in this study belonged to genotype I, with most of the samples clustering in subgenotype IA, while several unique amino acid variants were observed. The estimated mean substitution rate was 5.56×10(-4) substitutions / site / year, the time to the most recent common ancestor of genotype I isolates in
China was calculated to be around 180 years ago. Skyline plots showed the incidence of HAV went down gradually from the mid-1990s.
CONCLUSIONS: The evolution estimations were consistent with the laboratory and epidemiological results. Several isolates from
China showed amino acid changes close to the immunodominant sites, which needs to be further analyzed. The study results have indicated the effectiveness of improving economic and sanitation levels together with HAV vaccination to control HAV-related infections in
China.