中国大陆地区2013-2019年H7N9禽流感病毒神经氨酸酶基因特征分析  

Characteristic Analysis of Avian Influenza A (H7N9) Neuraminidase Gene of China's Mainland During 2013 to 2019

作　　者：范云燕[1] 欧嵩凤 汤洪洋[1] 陈敏玫[2] 康宁[2] Fan Yunyan;Ou Songfeng;Tang Hongyang;Chen Minmei;Kang Ning(Nanning Center for Disease Control and Prevention,Nanning,530023;Guangxi Center for Disease Control and Prevention,Nanning,530028)

机构地区：[1]南宁市疾病预防控制中心,南宁530023 [2]广西壮族自治区疾病预防控制中心,南宁530028

出　　处：《基因组学与应用生物学》2020年第5期1982-1989,共8页Genomics and Applied Biology

基　　金：广西壮族自治区卫生健康委员会自筹经费科研项目(Z2015457)资助。

摘　　要：分析中国大陆地区2013-2019年H7N9禽流感神经氨酸酶(NA)基因分子流行和遗传规律,为人感染H7N9禽流感防治提供科学依据。本研究从全球共享禽流感数据倡议组织(GISAID)数据库获得2013-2019年中国大陆地区人感染H7N9禽流感NA全长核苷酸序列。用MEGA7.0软件构建进化树,对NA基因同源性、糖基化位点和耐药位点变异进行分析,共获得1172条序列,其主要分布于五波疫情的毒株中。其中第五波疫情毒株数最多,占总数的34.27%,分布于大陆地区26个省份(自治区,直辖市)。1172份毒株NA基因在系统发育树上聚集为长江三角洲谱系和珠江三角洲谱系。同源性分析显示,2013年疫苗株与随后几年流行株匹配度越来越低,而2016年疫苗株匹配度也呈下降趋势。1167份毒株NA基因均缺失69~73 QISNT序列;与疫苗株相比,NA 5个糖基化位点因突变而消失;在6个耐药位点中均能检测到突变毒株。耐药位点中R292K替换频率最高,这种突变在第一至三波疫情中已出现,而在第五波疫情中数量增加明显。与前四波相比,在第五波疫情毒株中NA有更多的糖基化位点和耐药位点发生突变,这表明我国第五波H7N9病毒NA遗传多样性更广,变异频率更高,可能是第五波疫情感染人数增加、药物治疗效果降低的原因之一。To analyze the molecular epidemiology and genetic laws of Neuraminidase(NA)gene of Avian Influenza A(H7N9)in China's Mainland during 2013 to 2019,and to provide scientific basis for the prevention and treatment of human infection with avian influenza A(H7N9),the full-length nucleotide sequences of avian influenza A(H7N9)in China's Mainland from 2013 to 2019 were obtained from the Global Initiative on Sharing All Influenza Data(GISAID).The phylogenetic trees based on NA sequences of H7N9 were constructed by MEGA 7.0 software,and the homology,glycosylation sites and drug-resistance sites of NA genes were analyzed.A total of 1172 strains,which were mainly distributed in the 5 waves stains,were obtained.The wave 5 accounting for 34.27%of the total virus strains had the most virulent strains,which were distributed in 26 provinces autonomous regions,municipalities in China's Mainland.1172 NA genes were clustered in Yangtze River delta lineages and the Pearl River delta lineages.The homology analysis indicated that the vaccine strains from 2013 were less matched up with the active strains in the subsequent years,and the vaccine strains from 2016 also showed a downward trend.1167 strains were lack of 69~73 QISNT sequence in NA stalk.Compared with the vaccine strain,five glycosylation sites of NA disappeared,and mutation were detected in six drug-resistant sites.The R292 K mutation frequency was the highest in all drug-resistant sites,and this mutation had occurred in wave 1~3,while the number of which increased significantly in wave 5.Compared with the previous waves,there were more glycation sites and drug-resistance sites mutation in NA in wave 5,indicating that the larger genetic diversity and higher mutation frequency of virus NA in wave 5,which may account for the sharp increase in human infections with this virus in wave 5 but a decreased efficacy of drug treatment.

关 键 词：H7N9禽流感病毒 神经氨酸酶基因 特征分析 

分 类 号：S852.65[农业科学—基础兽医学]