人感染高致病性H5N6禽流感病毒表面糖蛋白分子进化特征  

Molecular characteristic of the two surface glycoproteins of highly pathogenic avian influenza A H5N6 viruses from human,2014-2018,China

作　　者：顾宏伟 祁贤[2] 陈磊垚[1] 鲍倡俊[2] GU Hong-wei;QI Xian;CHEN Lei-yao;BAO Chang-jun(Nanjing Integrated Traditional Chinese and Western Medicine Hospital,Nanjing 210009,China;Jiangsu Provincial Center for Disease Control and Prevention,Nanjing 210009,China)

机构地区：[1]南京市中西医结合医院,南京210014 [2]江苏省疾病预防控制中心,南京210009

出　　处：《中华疾病控制杂志》2020年第4期456-461,共6页Chinese Journal of Disease Control & Prevention

基　　金：江苏省重大科技示范项目(BE2017749),江苏省医学重点学科(ZDXKA2016008)。

摘　　要：目的对19例人感染高致病性H5N6禽流感病毒的血凝素(hemagglutinin,HA)和神经氨酸酶(neuraminidase,NA)蛋白进行分子进化分析。方法运用下一代测序平台对病毒分离物进行全基因组测序,从美国国家生物技术信息中心(national center for biotechnology information,NCBI)和全球流感序列数据库(global initiative on sharing avian influenza data,GISAID)下载参考序列,利用Blasts、Mega 6.1及Clustal X 2.1等软件进行序列分析。结果2014-2018年中国共发生23例人感染H5N6禽流感病毒病例。对19个病例的H5N6病毒的HA和NA基因进行进化分析。HA进化分析显示病毒都属于Clade 2.3.4.4,其中涉及17个病例的病毒属于Group C;首例H5N6病例毒株(A/Sichuan/26221/2014)属于Group D;福建一个病例(A/Fujian-Sanyuan/21099/2017)属于Group B。所有19个病例的病毒HA蛋白的裂解位点含有多个碱性氨基酸。所有病毒的HA蛋白的受体结合位点226~228位氨基酸是QS(R)G(氨基酸排序以H3-HA为准),理论上对禽类受体α2-3半乳糖苷唾液酸(SAα2-3Gal)有嗜性。18病例病毒的HA蛋白发生了T160A的突变,导致在158N位点失去糖基化。除了A/Sichuan/26221/2014外,18个病例的病毒NA蛋白在58~68位缺失了10个氨基酸。9个病例的病毒PB2蛋白发生E627K突变。结论2014-2018年间中国人感染H5N6病毒进化活跃,具有明显的基因多样性,需要加强对病毒分子进化的监测。Objective To analyze the molecular characteristic of hemagglutinin(HA)and neuraminidase(NA)proteins of highly pathogenic avian influenza H5 N6 viruses from 19 human cases.Methods Whole-genome sequences of original specimen and virus isolates were obtained by next-generation sequencing technology.Reference sequence information was collected from national center for biotechnology information(NCBI)and global initiative on sharing avian influenza data(GISAID)database.Pairwise sequence alignments and phylogenetic analysis were performed by Blasts,Clustal X 2.1 and Mega 6.1 softwares.Results A total of 23 cases of human infection with H5 N6 avian influenza virus occurred in China from 2014 to 2018.The HA and NA genes of H5 N6 virus from 19 cases were analyzed.HA evolutionary analysis showed that viruses belonged to Clade 2.3.4.4,of which 17 cases belonged to Group C;the first H5 N6 strain(A/Sichuan/26221/2014)belonged to Group D;and a Fujian case strain(A/Fujian-Sanyuan/21099/2017)belonged to Group B.The cleavage sites of HA protein of 29 strains of viruses in all 19 cases contained multiple basic amino acids.The 226-228 amino acids at the receptor binding sites of HA proteins of all viruses were QS(R)G(amino acids are sequenced according to the HA sequence of H3 subtype).In addition to one case in Guangzhou in 2014,the HA protein of 18 isolates mutated in T160 A,resulting in loss of glycosylation at 158 N site.In addition to A/Sichuan/26221/2014,10 amino acids were deleted in 58-68 sites of NA proteins of strains from 18 cases.E627 K mutation occurred in 17 strains of virus PB2 protein from 9 cases.Conclusions From 2014 to 2018,the evolution of H5 N6 virus infection in China is active,and there is obvious genetic diversity.It is necessary to strengthen the monitoring of the evolution of H5 N6 viruses in China.

关 键 词：禽流感病毒 H5N6亚型 人感染病例 分子进化 

分 类 号：R181.1[医药卫生—流行病学]