| 摘要: |
| 目的:探讨2009年新型甲型流感病毒(A/H1N1)基质蛋白(M)及核蛋白(NP)基因的进化规律。方法:从NCBI数据库下载147条甲型H1N1流感病毒M基因及NP基因序列,采用Molecular Evolutionary Genetics Analysis version 4.0(MEGA4.0)软件对M基因和NP基因序列进行比对,并用NJ法构建进化树,同时采用Epi Info软件分析1918~2009年人H1N1病毒的M基因和NP基因序列进化距离的线性趋势。采用MEGA4.0软件对M2蛋白氨基酸序列进行比对。结果:不同地区的2009年新型甲型H1N1流感病毒M基因、NP基因同源性高,但与历史上流行的H1N1流感病毒M基因、NP基因差异较大,且M基因进化距离随分离年限变化的趋势性检验结果有统计学意义(Ptrend=0.001)。2009年新型甲型A/H1N1流感病毒M2蛋白与1918~2008年人A/H1N1病毒M2蛋白氨基酸序列进行比对,结果显示在第11、43、54、57、77、78氨基酸位点发生了改变；与猪、禽A/H1N1的M2蛋白氨基酸序列进行比对,结果显示仅在第43、77位氨基酸位点发生改变。结论:2009年新型甲型A/H1N1流感病毒NP基因片段较以往流行的人H1N1流感病毒NP基因发生了改变；M2蛋白位于胞外编码区的第11位氨基酸、位于TM结构域的第43位氨基酸突变可能导致了新型甲型A/H1N1流感病毒对金刚烷胺类特异性抗病毒药物产生耐药。 |
| 关键词: H1N1甲型流感病毒 M基因 NP基因 进化 |
| DOI：10.3724/SP.J.1008.2009.0622 |
| 投稿时间：2009-05-21修订日期：2009-06-01 |
| 基金项目:军队“十一五”科技攻关计划(06G65),上海市自然科学基金(07ZR14141),上海市公共卫生“三年行动计划”重点学科项目(08GWZX0201,08GWZX0101). |
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| Molecular evolutionary analysis of matrix protein and nucleoprotein genes of novel influenza virus A/H1N1 in 2009 pandemic |
| HAN Yi-fang,XIE Jia-xin,YIN Jian-hua,LI Shu-hua,ZHANG Hong-wei,HAN Lei,LU Wen-ying,CAO Guang-wen* |
| (Department of Epidemiology,College of Basic Medical Sciences,Second Military Medical University,Shanghai 200433,China) |
| Abstract: |
| Objective:To analyze evolutionary characteristics of the matrix protein (M) and nucleoprotein (NP) genes of influenza virus A/H1N1 in 2009 pandemic.Methods: The M and NP genes of A/H1N1 viruses were downloaded from NCBI database.MEGA4.0 software and NJ method were used for sequence alignment,protein sequence alignment,and the phylogenetic tree construction.Meanwhile,Epi Info software was used to analyze the linear trend of evolutionary distance of the M and NP genes of human H1N1 strains isolated during 1918 to 2009.Results: The M and NP gene sequences were similar among the novel A/H1N1 viruses,but different from those of the previous influenza H1N1 viruses.Using reference sequences of human H1N1 strains isolated during 1918 to 2008,we found that changes in evolutionary distances of the M genes between novel A/H1N1 strains and each of the reference A/H1N1 strains increased with increasing year intervals (Ptrend = 0.001).Compared with the amino acid sequence of M2 protein of reference human A/H1N1 virus strains isolated during 1918 to 2008,the novel A/H1N1 viruses had the amino acid substitutions at 6 sites: 11,43,54,57,77,and 78.Compared with swine and avian A/H1N1,the novel A/H1N1 virus only had the amino acid substitutions at 43 and 77.Conclusion: The NP gene of novel A/H1N1 virus,which is routinely considered as a conserved sequence,is different from those of the previously isolated human H1N1 influenza viruses; the related mechanisms and consequences on viral activity remain to be elucidated.The substitution to threonine at 11 and 43 amino acids of M2 protein might contribute to amantadine resistance of the novel H1N1 virus pandemic in 2009. |
| Key words: H1N1 subtype influenza A virus M gene NP gene evolution |
