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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EpiInfo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。
Objective: To investigate the evolution of the matrix protein (M) and nucleoprotein (NP) genes of new type A (H1N1) virus in 2009. Methods: A total of 147 M and NP gene sequences of Influenza A (H1N1) virus were downloaded from the NCBI database. M and NP gene sequences were aligned by Molecular Evolutionary Genetics Analysis version 4.0 (MEGA4.0) Meanwhile, the linear trend of evolutionary distance of M gene and NP gene of human H1N1 virus from 1918 to 2009 was analyzed by EpiInfo software. The amino acid sequence of M2 protein was aligned by MEGA 4.0 software. Results: The homology of M gene and NP gene of new influenza A (H1N1) virus in 2009 in different areas was high. However, the M gene and NP gene of H1N1 influenza virus were quite different from those in H1N1 influenza virus in history. The evolutionary distance of M gene changed with the years of isolation The trend test results were statistically significant (Ptrend = 0.001). The amino acid sequence of the M2 protein of the new type A / H1N1 influenza virus in 2009 and the human A / H1N1 virus M2 protein in the period of 1918-2008 showed that at the 11th, 43th, 54th, 57th, 77th and 78th amino acid positions The amino acid sequence of M2 protein of pig / bird A / H1N1 was changed. The results showed that only the amino acid at positions 43 and 47 changed. CONCLUSION: The NP gene fragment of new influenza A / H1N1 influenza virus was changed from that of human influenza virus H1N1 in 2009. The M2 protein is located at the 11th amino acid in the extracellular coding region and is located at the 43rd position of the TM domain Amino acid mutations may have led to the emergence of a new type A / H1N1 influenza virus that is resistant to amantadine-specific antiviral drugs.