湖南省2006--2009年人感染高致病性禽流感病毒(H5N1)分子特征研究

黄一伟; 董丽波; 李俊华; 刘运芝; 高立冬; 张红; 陈长; 胡世雄; 李芳彩; 舒跃龙

Abstract

黄一伟,董丽波,李俊华,刘运芝,高立冬,张红,陈长,胡世雄,李芳彩,舒跃龙.湖南省2006--2009年人感染高致病性禽流感病毒(H5N1)分子特征研究[J].Chinese journal of Epidemiology,2011,32(7):709-715

湖南省2006--2009年人感染高致病性禽流感病毒(H5N1)分子特征研究

Molecular eharacterization of highly pathogenic avian influenza A(H5N1)viruses isolated from humans in Hunan province，2006—2009

Received:January 05, 2011

DOI：

KeyWord: 禽流感病毒H5N1 基因特性

English Key Word: Avian influenza virus H5Nl Genetic characterization

FundProject:国家科技重大专项课题(2008ZX 10004—013);湖南省卫生厅科研基金课题(A2007008)

Author Name	Affiliation	E-mail
HUANG Yi-wei	Hunan Provincial Center for Disease Control and Prevention, Changsha 410005, China
DONG Li-bo	National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention
LI Jun-hua	Hunan Provincial Center for Disease Control and Prevention, Changsha 410005, China
LIU Yun-zhi	Hunan Provincial Center for Disease Control and Prevention, Changsha 410005, China
GAO Li-dong	Hunan Provincial Center for Disease Control and Prevention, Changsha 410005, China
ZHANG Hong	Hunan Provincial Center for Disease Control and Prevention, Changsha 410005, China
CHEN Zhang	Hunan Provincial Center for Disease Control and Prevention, Changsha 410005, China
HU Shi-xiong	Hunan Provincial Center for Disease Control and Prevention, Changsha 410005, China
LI Fang-cai	Hunan Provincial Center for Disease Control and Prevention, Changsha 410005, China
SHU Yue-long	National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention	shu@enie．org．cn

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Abstract:

目的分析湖南省2006--2009年4例人感染高致病性禽流感病例感染病毒的可能来源、基因重配情况以及分子特征。方法鸡胚分离核酸检测H5N1病毒阳性标本，获得高致病性H5N1病毒，对病毒进行全基因组序列测定，采用BLAST和MEGA4．0进行同源性比对、基因进化分析和各基因分子特征分析。结果4株病毒的基因片段均为禽源，并未发现与人季节性流感病毒之间发生蕈配，且与当地禽类中分离的病毒高度同源。全基因组进化树分析显示，4株病毒在分支2．3．4中，2株为基因型V、2株为新的基因型。分子特征分析屁示，4株病毒的血凝素(HA)分子裂解位点均为PLRERRKR／G，均出现A160T位点突变，神经氨酸酶(NA)分子49—68位均出现20个氨基酸(an)缺失，非结构蛋白1(NSI)分子80～84位均出现5个an的缺失。在HA分子大部分位点，4株病毒仍然表现出与禽类受体的亲和性，HN／I／09和HN／2／09出现可能使病毒对d一2，6连接的唾液酸人类受体的亲和性增强的T192I突变。HN／1108的PB2基因出现增加小鼠致病力的D701N改变。耐药性基因片段分析显示，4株病毒对金刚烷胺和奥司他韦均敏感。结论2006--2009年湖南省4株人感染高致病性禽流感病毒(H5N1)为禽源，但存在多种基因型，而且发生了部分位点的突变。

English Abstract:

Objective To understand the possible origins．genetic re-assortment and molecular characterization of 4 highly pathogenic avian influenza A(H5N 1)vimses isolated from humans in Harian province．between 2006 and 2009．Methods H5Nl PCR test-positive specimens were inoculated in embryonated eggs while H5Nl virus was isolated and genomes sequenced． Genome homology and genetic molecular characterization were analyzed bv BLAST and MEGA 4．0．Results An gene segments of the 4 viruses were avian in origin．No re-assortment was found between avian influenza A(H5N 1)vimses and human seasonal influenza viruses．Viruses that isolated from domestic poultry shared high similarity with the 4 human viruses in gene homology．Data from the whole genome phylogenetic analysis showed that the 4 viruses were in clade 2．3．4． while 2 viruses belonged to genotype V，and another 2 were new genotypes．Results from molecular characterization showed that amino acid sequences of HA cleavage sitc of the 4 viruses were PLRERRKR／G．All 4 viruses had A160T mutation in HA．a 20 amino acid deletion in the neuraminidase(NA)stalk at position 49-68．and a 5 amino acid deletion in the non—structural protein l(NS 1)．Most sites in the HA molecules showed that the viruses preferentially bound to avian influenza virus receptor．However，T192I mutation that might enhance thea2，6一linked sialic acid human influenza receptor binding had emerged in HN／I／09 and HN／2／09．D70 l N mutation of PB2 that increased the virulence in mice was foand in HN／I／08．Analysis on drug resistance gene amino acid showed that all 4 viruses were sensitive to amantadine and oseltamivir．Conclusion Highly pathogenic avian influenzaA(H5N 1)viruses isolated from humans in Hunan province from 2006 to 2009 were avian in origin。and the 4 viruses belonged to different genotypes．Some mutations that related to virulence and receptor binding positions had emerged in some of the strains．

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