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目的探讨甲型流感病毒不同亚型血凝素(HA)基因的历史进化演变规律。方法从NCBI数据库中收集到140多个甲型不同亚型流感病毒株,涵盖人、猪、禽三个物种的不同历史时期及不同地区的病毒的HA基因序列。利用PHYLIP软件包对所选序列进行基因进化分析,构建NJ进化树;采用Clustal X软件对与2009年新型甲型H1N1流感病毒聚在同一进化分支的其他猪流感病毒的HA基因的氨基酸序列进行分析。结果人类三种主要亚型H1N1、H2N2和H3N2具有不同的时间分布特征,表现为1957年之前,主要流行株为H1N1亚型,1957-1968年为H2N2亚型,从1968年起主要流行株为H3N2亚型和H1N1亚型共同在人间传播;从20世纪80年代起流感病毒物种间隔离现象逐渐模糊,陆续出现了猪/禽/人病毒混合感染的病例,H5N1亚型流感病毒物种间隔离最弱;2009年新型甲型流感病毒与猪H1N1流感病毒聚在一支,提示2009年波及全球的新型甲型流感病毒为猪H1N1亚型病毒造成的;氨基酸序列分析显示:2009年新型甲型流感病毒HA基因中共有13个特有的氨基酸变异位点,提示这些位点可能参与了猪和人H1N1亚型病毒物种隔离屏障的限制,其功能尚需进一步确定。结论甲型流感病毒亚型间存在相互演化关系,不同物种间病毒混合感染的发生,病毒变异的机会增加。
Objective To investigate the evolutionary history of the hemagglutinin (HA) gene of different subtypes of influenza A virus. Methods A total of more than 140 Influenza A subtypes were collected from the NCBI database, covering the HA gene sequences of human, pig and poultry in different historical periods and in different regions. The phylogenetic analysis of the selected sequences was carried out using the PHYLIP software package to construct the NJ phylogenetic tree. The amino acid sequence of HA gene of other swine influenza viruses clustered in the same evolutionary branch with 2009 new type A H1N1 influenza virus was analyzed by Clustal X software . Results The three major subtypes of human H1N1, H2N2 and H3N2 had different time distribution characteristics. Before 1957, the main epidemic strains were H1N1 subtype and 1957-1968 H2N2 subtype. Since 1968, the main epidemic strains were H3N2 subtypes and H1N1 subtypes are commonly transmitted in humans. Since the 1980s, the isolation of influenza virus species has been gradually blurred, and the cases of mixed pig / fowl / human virus infection successively appear. The isolates of H5N1 subtype influenza virus Weak; in 2009 a new influenza virus and swine H1N1 influenza virus together, suggesting that in 2009 the world’s new influenza A virus caused by the swine H1N1 subtype virus; amino acid sequence analysis showed that: 2009 new influenza A There are 13 unique amino acid variation sites in the HA gene of the virus, suggesting that these sites may be involved in the isolation barrier of the H1N1 subtype virus in pigs and humans, and their function needs to be further identified. Conclusions The subtypes of influenza A virus have evolutionary relationship with each other. The occurrence of virus mixed infection among different species and the chance of virus mutation increase.