Huang Ping, Zou Li-Rong, Fan Ling, Li Hui, Chen Qiu-Xia, Yu Shou-Yi, Ke Chang-Wen
Provincial Key Laboratory for Emergency Pathogen Detection,Center for Disease Control and Prevention of Guangdong Province, Guangzhou 510300, China.
Bing Du Xue Bao. 2007 Sep;23(5):371-6.
In order to reveal variation and evolution of M genes of human avian H5N1 influenza strains, the M genes of human avian H5N1 strains in Guangdong were sequenced and the M genes of global strains were searched out from Internet. They were analyzed by DNAStar 5. 0 and their revolutionary speeds were studied by means of combining the epidemiological data. It was found that M1 genes of 53 H5N1 strains and M2 genes of 51 strains during 1997-2006 were homologously classified into two groups: the strains from Hong Kong during 1997 (G I) were one group and the strains from Hong Kong, Vietnam, Thailand, Indonesia, China mainland, Turkey, Iraq, Azerbaijan, Egypt during 2003-2006 (G II ) were the another group. There were 20 substitutions of amino acids in M1 gene of all strains (7.94%, 20/252), where there were 9 amino acids in strains during 2003-2006 differing from the strains in 1997, meanwhile there were 22 substitutions of amino acids in M2 gene of all strains (22.7%, 22/97), where there were 4 amino acids in strains during 2003-2006 differing from the strains in 1997. In the synonymous variation, Ks values in M1 were 26.8 x 10(-6)-42.6 x 10(-6) Nt/d, and Ka values 4.39 x 10(-6)-6.98 x 10(-6) Nt/d, where there was more rapid speed of synonymous substitution than that of replacement, which showed that there existed less human immunological pressure and negative selective pressure by biological test. Ks values in M2 were 13.1 x 10(-6)-23.4 x 10(-6) Nt/ d, and Ka values 9.1 x 10(-6)-16.2 x 10(-6) Nt/d; where the ratios of Ks to Ka was 1.0-1.6 times as there was the neutral selective pressure in TL-676-05 strain. There was an amino acid substitution of S224, N in M1 gene of strains during 2003-2006 and an increas in a glycoprotein domain NSS224-226. The secondary structure of M2 protein varied as the substitution of C50 F of eight strains from Indonesia in 2005. The strains G I did not reemerge after Hong Kong human avian H5N1 influenza event. An increase of a glycoprotein domain NSS224-226 in M1 protein during 2003-2006 might be related with virus pathogenicity. Human avian H5N1 influenza M gene evolved frequently in nature, which might have an impact on its capacity of human-to-human transmission.
为揭示人感染H5N1禽流感病毒株M基因的变异与进化情况，对广东人感染H5N1禽流感病毒株的M基因进行测序，并从互联网上搜索全球病毒株的M基因。利用DNAStar 5.0软件对其进行分析，并结合流行病学数据研究其进化速度。结果发现，1997 - 2006年间53株H5N1病毒株的M1基因和51株病毒株的M2基因可同源分为两组：1997年来自香港的病毒株（G I组）为一组，2003 - 2006年来自香港、越南、泰国、印度尼西亚、中国大陆、土耳其、伊拉克、阿塞拜疆、埃及的病毒株（G II组）为另一组。所有病毒株M1基因有20个氨基酸替换（7.94%，20/252），其中2003 - 2006年病毒株与1997年病毒株相比有9个氨基酸不同；所有病毒株M2基因有22个氨基酸替换（22.7%，22/97），其中2003 - 2006年病毒株与1997年病毒株相比有4个氨基酸不同。在同义变异方面，M1基因的Ks值为26.8×10⁻⁶ - 42.6×10⁻⁶ Nt/d，Ka值为4.39×10⁻⁶ - 6.98×10⁻⁶ Nt/d，同义替换速度快于替换速度，表明通过生物学检测存在较小的人体免疫压力和负选择压力。M2基因的Ks值为13.1×10⁻⁶ - 23.4×10⁻⁶ Nt/d，Ka值为9.1×10⁻⁶ - 16.2×10⁻⁶ Nt/d；在TL - 676 - 05株中Ks与Ka的比值为1.0 - 1.6倍，存在中性选择压力。2003 - 2006年病毒株M1基因有S224、N氨基酸替换，糖蛋白结构域NSS224 - 226增加。2005年来自印度尼西亚的8株病毒株C50F替换导致M2蛋白二级结构发生变化。香港人感染H5N1禽流感事件后G I组病毒株未再出现。2003 - 2006年M1蛋白糖蛋白结构域NSS224 - 226增加可能与病毒致病性有关。人感染H5N1禽流感M基因在自然环境中频繁进化，可能影响其人际传播能力。
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