两株H9N2亚型禽流感病毒的全基因组序列测定及其对小鼠的感染性研究
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摘要
为了解2015年广西地区活禽市场中的两株鸡源H9亚型禽流感病毒(AIV)A/chicken/GX/S30272/2015(H9N2)(简称GX/272/15株)和A/chicken/GX/S30825/2015(H9N2)(GX/825/15株)的生物学特性,本研究对其进行了全基因组序列测定和小鼠的感染性试验。核苷酸序列分析表明,两株病毒的HA基因发生了I~(155)T、H~(183)N、A~(190)T和Q~(226)L突变,这些突变与增强病毒的人源受体结合特性密切相关。遗传演化关系表明,两株病毒的HA基因均属于欧亚分支Beijing/1/94谱系。GX/272/15株的8个基因节段和GX/825/15株的HA节段来源于H9N2 AIV,GX/825/15株的其余7个基因节段分别来源于H4N2、H10N6、H7N9、H7N1、H9N2、H6N6和H3N2多种不同亚型的AIV。两株病毒均可感染小鼠,且均不需要经过适应即可在小鼠的鼻甲内进行复制。但仅GX/825/15可以在小鼠的肺脏内复制。两株病毒均未造成小鼠死亡,仅引起小鼠体重的轻微变化,对小鼠呈低致病力。本研究结果表明,H9N2亚型AIV能够感染哺乳动物,应加强后续分离病毒对人类健康危害性的评估。
To investigate the biological characteristics of two H9N2 subtype avian influenza viruses(AIVs) of GX/272/15 and GX/825/15 isolated from chickens in live poultry markets in Guangxi in 2015, the whole genomic sequence were analyzed and the infectivity was evaluated in BALB/cmice. The nucleotide sequence analyses found that the mutations of I~(155)T, H~(183)N, A~(190)T and Q~(226)L occurred in HA of the two isolates, which were closely related to enhancing human-type receptor binding specificity of the viruses in HA. Phylogenetic relationships indicated that the HA genes of the two isolates belonged to Beijing/1/94 sublineage of the Eurasian lineage. The eight segments of GX/272/15 and the HA genes of GX/825/15 originated from the H9 AIVs, the other seven segments of GX/825/15 derived from diverse subtypes viruses including H4N2, H10N6, H7N9, H7N1, H9N2, H6N6 and H3N2 AIVs. In addition, both the viruses were able to infect mice and replicate in the upper respiratory tract of infected mice without adaptation. However, only GX/825/15 could be detected in the lungs of mice. The two viruses did not cause the death ofmice, only caused slight changes in body weight of mice during the observation period, indicating that the two HPN2 viruses were low pathogenicity to mice. These results demonstrated that the H9N2 AIVs had the ability to infect mammals and the potential harmfulness of H9N2 subtype AIVs to human health need to be further evaluated.
To investigate the biological characteristics of two H9N2 subtype avian influenza viruses(AIVs) of GX/272/15 and GX/825/15 isolated from chickens in live poultry markets in Guangxi in 2015, the whole genomic sequence were analyzed and the infectivity was evaluated in BALB/cmice. The nucleotide sequence analyses found that the mutations of I~(155)T, H~(183)N, A~(190)T and Q~(226)L occurred in HA of the two isolates, which were closely related to enhancing human-type receptor binding specificity of the viruses in HA. Phylogenetic relationships indicated that the HA genes of the two isolates belonged to Beijing/1/94 sublineage of the Eurasian lineage. The eight segments of GX/272/15 and the HA genes of GX/825/15 originated from the H9 AIVs, the other seven segments of GX/825/15 derived from diverse subtypes viruses including H4N2, H10N6, H7N9, H7N1, H9N2, H6N6 and H3N2 AIVs. In addition, both the viruses were able to infect mice and replicate in the upper respiratory tract of infected mice without adaptation. However, only GX/825/15 could be detected in the lungs of mice. The two viruses did not cause the death ofmice, only caused slight changes in body weight of mice during the observation period, indicating that the two HPN2 viruses were low pathogenicity to mice. These results demonstrated that the H9N2 AIVs had the ability to infect mammals and the potential harmfulness of H9N2 subtype AIVs to human health need to be further evaluated.
引文
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[4]Wan Hong-quan,Sorrell E M,Song Hai-chen,et al.Replication and transmission of H9N2 influenza viruses in ferrets:evaluation of pandemic potential[J].PLo S One,2008,3(8):e2923.
[5]Li Cheng-jun,Yu Kang-zhen,Tian Guo-bin,et al.Evolution of H9N2 influenza viruses from domestic poultry in Mainland China[J].Virology,2005,340(1):70-83.
[6]Matrosovich M N,Krauss S,Webster R G.H9N2 Influenza A viruses from poultry in Asia have human virus-like receptorspecificity[J].Virology,2001,281(2):156-162.
[7]Jia Na,Liu Yun-xi,Zhang Jiu-song,et al.Serological reports of human infections of H7 and H9 avian influenza viruses innorthern China[J].J Clin Virol,2009,44(3):225-229.
[8]Li Xu-yong,Shi Jian-zhong,Chen Hua-lan,et al.Genetics,receptor binding property and transmissibility in mammals of naturally isolated H9N2 avian influenza viruses[J].PLo S Pathog,2014,10(11):1-12.
[9]Shaw M,Gregory V,Cameron K,et al.Avian-to-human transmission of H9N2 subtype influenza A viruses:Relationship between H9N2 and H5N1 human isolates[J].PNAS USA,2000,97(17):9654-9658.
[10]Yu Xin-fen,Jin Tao,Cui Yu-jun,et al.Influenza H7N9 and H9N2 viruses:coexistence in poultry linked to human H7N9 infection and genome characteristics[J].J Virol,2014,88(6):3423-3431.
[11]Deng Guo-hua,Shi Jian-zhong,Wang Jing,et al.Genetics,receptor binding,and virulence in mice of H10N8 influenza viruses isolated from ducks and chickens in live poultry markets in China[J].J Virol,2015,89(12):6506-6510.
[12]Gao Rong-bao,Cao Bin,Hu Yun-wen,et al.Human infection with a novel avian-origin influenza A(H7N9)virus[J].N Engl J Med,2013,368(20):1888-1897.
[13]Liu Ming-bin,Li Xiao-dan,Yuan Hui,et al.Genetic diversity of avian influenza A(H10N8)virus in live poultry markets and its association with human infections in China[J].Sci Rep,2015,5:7632.
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