摘要目的 揭示2011-2015年广东地区甲型H3N2毒株血凝素(HA)基因进化特征和变异特点.方法 采用时空抽样方法抽样,测定2011-2015年广东甲型H3N2毒株HA核苷酸序列,同时检索全球HA序列作为对照,采用MEGA5.05、BEAST v1.7.0和BioEdit7.1.3软件对HA基因核苷酸序列进行比对和分析.结果 广东48株H3 N2流感病毒的HA序列核苷酸同源性为96.4％～100.00％,2013-2015年广东H3 N2亚型流感病毒HA基因与南半球疫苗株A/Switzerland/9715293/2013的同源性为97.8％ ～98.7％,抗原性较为接近.序列系统进化分析显示,其进化规律都是沿着树枝主干随着时间推移向上延伸,广东毒株主要分布在3C.3a分支,2015年部分毒株出现在3C.2a分支.2011-2015年HA基因共出现1 16个氨基酸位点突变,其中12个氨基酸位点突变涉及4个抗原表位,N241D(N225D)和K192C突变发生在受体结合部位和其中的190螺旋区内.结论 2011-2015年广东甲型H3N2毒株HA抗原变异明显,抗原变异的积累可能出现抗原漂移和流感暴发,应该加强流感病原学监测,及时发现新的流感变异株,为流感防控和降低流感对公众健康危害提供科学依据.

abstractsObjective To study the evolution and variation of the genes encoding hemagglutinin (HA) proteins of H3N2 influenza virus strains prevalent in Guangdong during 2011-2015.Methods Fortyeight H3N2 influenza virus strains prevalent in Guangdong during 2011-2015 were recruited in this study by using time-space sampling.The nucleotide sequences of HA genes of those strains were sequenced and compared with those of the H3N2 influenza virus strains prevalent worldwide.The mutations and antigenic variations in HA genes of Guangdong strains were analyzed by MEGA 5.05,BEAST v1.7.0 and BioEdit7.1.3.Results The 48 H3N2 influenza virus strains prevalent in Guangdong shared 96.4％-100.00％ homologies in nucleotide sequences.The Guangdong strains isolated during 2013-2015 shared 97.8％-98.7％ homologies in nucleotide sequences with the southern hemisphere vaccine strain A/Switzerland/9715293/2013.Pbylogenetic analysis showed that the evolution was upward along the main branch over time.The Guangdong strains mainly distributed in clade 3C.3a with some of the 2015 strains in clade 3C.2a.A total of 330 nucleotide mutations were detected in the HA genes of H3N2 influenza virus strains prevalent during 2011-2015 as compared with the HA gene of the vaccine strain A/Texas/50/2012,resulting in 116 amino acid mutations with 12 of them associating with 4 epitope mutations.The N241D (N225D) and K192C mutations located in the receptor binding sites (RBS) and the 190 helix of RBS,respectively.Conclusion Amino acid mutations occurred in the antigenic epitopes of HA proteins of H3N2 influenza virus strains prevalent in Guangdong province during 2011-2015,which might give rise to antigenic drift resulting in the outbreak of influenza.Thus,it is necessary to strengthen the surveillance for influenza pathogens.