一株H5N3亚型禽流感病毒全基因组序列分析及其对小鼠的感染性研究
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摘要
为了解H5N3亚型流感病毒的生物学特性,本研究对2017年浙江省分离到的一株H5N3亚型禽流感病毒(AIV)[DK/ZJ/S1368/2017 (H5N3)]进行了遗传演化分析及小鼠感染性实验。遗传演化分析结果显示,该株病毒的HA蛋白裂解位点处仅含一个碱性氨基酸,属于低致病性AIV。同时,该病毒的血凝素(HA)基因与H5N7亚型流感病毒亲缘关系较近;聚合酶碱性蛋白2 (PB2)基因和核蛋白(NP)基因与H10N7亚型流感病毒亲缘关系较近;碱性聚合酶蛋白1 (PB1)基因与H1N1亚型流感病毒亲缘关系较近;酸性聚合酶蛋白(PA)基因与H6N2亚型流感病毒亲缘关系较近;神经氨酸酶(NA)基因与H10N3亚型流感病毒亲缘关系较近;基质蛋白(M)基因与H3N8亚型流感病毒亲缘关系较近;非结构蛋白(NS)基因与H1N1亚型流感病毒亲缘关系较近。表明其基因来源复杂。小鼠感染实验结果显示,该分离株无需提前适应即可以在小鼠肺脏和鼻甲中复制,小鼠感染病毒后无明显临床症状,与对照组相比其体质量变化不明显,表明该病毒对小鼠呈低致病性。本研究通过对该H5N3亚型AIV的生物学特性的分析,发现该病毒基因来源复杂,无需提前适应就可以在小鼠体内复制,具有感染哺乳动物的潜在威胁,提示应当持续加强对H5N3亚型AIV的监测和相关生物学特性的研究工作。
To investigate the biological characteristics of H5N3 subtype avian influenza virus(AIV), we in this study carried out genetic evolution analysis and mouse infection experiments on an H5N3 subtype AIV, A/duck/Zhejiang/S1368/2017(DK/ZJ/S1368/2017, H5N3) that was isolated from Zhejiang province in 2017. Genetic evolution analysis showed that there is only one basic amino acid at the cleavage site of HA protein, which is the signature for low pathogenic AIV. Meanwhile, the gene sources of this virus strain are complex. Its polymerase basic protein 2(PB2) and nucleoprotein(NP) gene are closely related to those of an H10N7 subtype AIV, and the closest relatives of the viral hemagglutinin(HA), polymerase basic protein 1(PB1),polymerase acidic protein(PA), neuraminidase(NA), matrix protein(M) and nonstructural protein(NS) gene are an H5N7, H1N1,H6N2, H10N3, H3N8, and H1N1 subtype AIV, respectively. The infection experiment demonstrated that the H5N3 AIV strain is low pathogenic to mice. It could replicate in the lungs and nasal turbinates of infected mice without prior adaptation, and that there were no obvious clinical symptoms and body weight change after the infection of the mice compared with the control group.Together, analysis of the biological characteristics of an H5N3 subtype AIV indicated that the sources of the viral gene segments are complex, and it could replicate in mice without prior adaptation, thus posing potential threat for human health. Our study therefore suggests that the surveillance of H5N3 subtype AIV and study on the related biological characteristics should be continuously strengthened.
To investigate the biological characteristics of H5N3 subtype avian influenza virus(AIV), we in this study carried out genetic evolution analysis and mouse infection experiments on an H5N3 subtype AIV, A/duck/Zhejiang/S1368/2017(DK/ZJ/S1368/2017, H5N3) that was isolated from Zhejiang province in 2017. Genetic evolution analysis showed that there is only one basic amino acid at the cleavage site of HA protein, which is the signature for low pathogenic AIV. Meanwhile, the gene sources of this virus strain are complex. Its polymerase basic protein 2(PB2) and nucleoprotein(NP) gene are closely related to those of an H10N7 subtype AIV, and the closest relatives of the viral hemagglutinin(HA), polymerase basic protein 1(PB1),polymerase acidic protein(PA), neuraminidase(NA), matrix protein(M) and nonstructural protein(NS) gene are an H5N7, H1N1,H6N2, H10N3, H3N8, and H1N1 subtype AIV, respectively. The infection experiment demonstrated that the H5N3 AIV strain is low pathogenic to mice. It could replicate in the lungs and nasal turbinates of infected mice without prior adaptation, and that there were no obvious clinical symptoms and body weight change after the infection of the mice compared with the control group.Together, analysis of the biological characteristics of an H5N3 subtype AIV indicated that the sources of the viral gene segments are complex, and it could replicate in mice without prior adaptation, thus posing potential threat for human health. Our study therefore suggests that the surveillance of H5N3 subtype AIV and study on the related biological characteristics should be continuously strengthened.
引文
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[2]陈化兰,于康震,步志高.一株鹅源高致病性禽流感病毒分离株血凝素基因的分析[J].中国农业科学,1999,32:87-92.
[3]Chen Hua-lan,Deng Guo-hua,Li Ze-jun,et al.The evolution of H5N1 influenza viruses in ducks in southern China[J].PNASUSA,2004,101:10452-10457.
[4]Chen Hua-lan,Li Yan-bing,Li Ze-jun,et al.Properties and dissemination of H5N1 viruses isolated during an influenza out-break in migratory waterfowl in western China[J].J Virol,2006,80:5976-5983.
[5]Balzli C,Lager K,Vincent A,et al.Susceptibility of swine to H5 and H7 low pathogenic Avian influenza viruses[J].Influenza Other Respir Viruses,2016,10(4):346-352.
[6]Becker W B.The isolation and classification of tern virus:Influenza virus A/tern/South Africa/1961[J].J Hyg(Lond),1966,64(3):309-320.
[7]Bi Y H,Mei K,Shi W,et al.Two novel reassortants of avian influenza A(H5N6)virus in China[J].J Gen Virol,2015,96:975-981.
[8]Yoon S W,Webby R J,Webster R G.Evolution and ecology of influenza A viruses[J].Curr Top Microbiol Immunol,2014,385:359-375.
[9]Lee M S,Chen L H,Chen Y P,et al.Highly pathogenic avian influenza viruses H5N2,H5N3,and H5N8 in Taiwan in 2015[J].Vet Microbiol,1996,187:50-57.
[10]Gao Rong-bao,Cao Bin,Hu Yun-Wen,et al.Human infection with a novel avian-origin influenza A(H7N9)virus[J].N Engl JMed,2013,368:1888-1897.
[11]Olsen C.The emergence of novel swine influenza viruses in North America[J].Virus Res,2002,85:199-210.
[12]Vincent A L,Lager K M,Lekcharoensuk P,et al.Evaluation of hemagglutinin subtype 1 swine influenza viruses from the United States[J].Vet Microbiol,2006,118:212-222.
[13]Garten R J,Davis C T,Russell C A,et al.Antigenic and genetic characteristics of swine-origin 2009 A(H1N1)influenza viruses circulating in humans[J].Sciences,2009,325:197-201.
[14]Shi Jian-Zhong,Deng Guo-Hua,Liu Pei-Hong,et al.Isolation and characterization of H7N9 viruses from live poultry markets-implication of the source of current H7N9 infection in humans[J].Chin Sci Bullet,2013,58:1857-1863.