HTN9禽流感病毒人感染株与禽源株基因组差异分析研究

目的对比分析人和活禽市场来源禽分离到的HTN9禽流感病毒基因组差异；为流行季节活禽市场管理提供依据。方法采集实验室确诊和有禽类接触史的HTN9病毒感染患者的咽拭子和痰标本，采用RT—PCR检测病毒的M、H7和N9基因，采用MDCK细胞培养病毒。对有流行病学关联的活禽市场收集了30份禽类泄殖腔拭子标本并接种于鸡胚。通过测序对从人和鸡分离到的病毒进行鉴定和分型，并对病毒的8个基因片段进行分析。结果患者感染毒株基因序列与从当地一农贸市场鸡中分离到的HTN9禽流感病毒基因序列同源。所有的病毒基因片段属于禽源性，从患者体内分离到的病毒株出现了H7基因Oln226Leu和Gly186Val替换（这有可能增加了病毒与人呼吸道上皮细胞唾液酸a-2，6型受体的亲和力）和PB2基因AspTOIAsn突变（该突变与禽流感病毒的哺乳动物适应性有关）。结论HTN9禽流感病毒出现了适应性变异，可从禽向人跨种传播。因其对家禽没有致病性，导致活禽交易不止，禽流感威胁不息，为有效控制禽类HTN9病毒进一步感染人并引发大流行，流行期间有必要采取一些如临时关闭活禽市场和综合性监测等有效措施。

Objective Comparative analyze the difference characteristic of virus genomics that isolate from H7N9 virus infected patients and live poultry market avians.Provide evidance for the epidmic season live poultry market management. Methods：We took throat and sputum samples, used RT-PCR to detect M, H7, and N9 genes, and cultured samples in Madin-Darby canine kidney cells. Collected cloacal swabs from 30 birds from epidemiologically linked wet markets and inoculated embryonated chicken eggs with the samples.identified and subtyped by whole gene sequencing done for one human and one chicken isolate. We characterised and phylogenetically analysed the eight gene segments of the viruses in the patient＇s and the chicken＇s isolates. Results：The viral isolate from the patient was closely similar to that from an epidemiologically linked market chicken. All viralgene segments were of avian origin, virus strains isolated from patients noted Gln226Leu and Gly186Val substitutions in human virus H7 （associated with increased affinity for a-2,6-1inked sialic acid receptors） and the PB2 Asp701Asn mutation （associated with mammalian adaptation）. Conclusion：Cross species poultry-to-person transmission of H7N9 virus is associated with its adaptive mutation,because of its low pathogenic avian influenza, the restless of Live poultry trade more than the threat of avian influenza, Aggressive intervention to block further animal-to-person transmission in live poultry markets, Temporary closure of live bird markets and comprehensive programmes of surveillance to control H7N9 virus infection in poultry seem necessary to halt evolution of the virus into a pandemic agent.