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2021年4月我国江苏确诊全球第一例人感染H10N3禽流感病例，研究我国活禽市场H10N3亚型禽流感病毒（Avian influenza virus, AIV）的遗传多样性和分子特征，将为理解人感染H10N3病毒的进化来源、评估其溢出风险提供理论依据。为此，2021年6-12月我们对安徽地区活禽市场销售家禽及环境中H10N3 AIV进行实时荧光定量RT-PCR检测，共分离鉴定到6株H10N3病毒（AH01-AH06），其中1株为11月份环境样本分离株，其余5株为6月、11月和12月鸡咽拭子分离株。高通量测序和生物信息学分析表明，同一活禽市场分离到的毒株表现出一定的遗传多样性和重配模式差异：4株H10N3分离株（AH01-AH04）间核苷酸同源性均高于99.00%，而A/chicken/Anhui/11-30-YHZGS024-O/2021(AH05)株的MP基因片段和A/chicken/Anhui/06-26-YHZGS006-O/2021(AH06)株的PA、MP基因片段与其他分离株的核苷酸同源性较低，均低于97.04%。系统发育分析显示，本研究6株H10N3分离株与人源H10N3病毒的HA和NA基因均位于欧亚进化分支，它们的内部基因都来自H9N2亚型AIV。特别是分离株AH06与人感染H10N3病毒八个基因均位于同一进化分支，而分离株AH01-AH05的PA基因与人感染H3N8和H9N2毒株、MP基因与人感染H9N2毒株的亲缘关系较近。分子遗传特征分析显示，6株H10N3 AIV的血凝素蛋白均携带G228S等哺乳动物适应性突变，提高了对人源受体的结合能力。综上，本研究证实了禽源H10N3病毒在安徽省活禽市场的持续流行，揭示了禽源H10N3病毒的遗传多样性以及新型感染人的H10N3在我国家禽中传播，强调其携带多个哺乳动物适应性突变，为评估H10N3 AIV潜在公共卫生风险提供了理论依据。
Abstract：In April 2021, the first human case of infection by the H10N3 subtype avian influenza virus(AIV) was identified in Jiangsu, China. The genetic diversity and molecular characterizations of H10N3 subtype AIV from live-poultry markets in China were studied. This strategy could enable understanding of the evolutionary origin of human-infecting H10N3 AIV and assessment of its spillover risk from poultry to humans. From June to December 2021, real-time reverse transcription-quantitative polymerase chain reactions were undertaken to detect H10N3 subtype AIV in poultry markets and environments in Anhui, China. Six strains(AH01–AH06) of H10N3 subtype AIV were isolated and identified. The whole-genome sequences of these viruses were amplified by high-throughput sequencing, and their genetic characterizations were analyzed. One of the six H10N3 isolates was found in an environmental sample collected in November 2021, and the remaining five were from chicken-throat swabs collected in June, November, and December 2021. Strains isolated from the same live-poultry market exhibited genetic diversity and differences in reassortment patterns. Among the six H10N3isolates, the eight gene segments of four isolates(AH01 – AH04) had nucleotide homology >99.00%. The PA gene segment of A/chicken/Anhui/11-30-YHZGS024-O/2021(AH05), and the PA and MP gene segments of A/chicken/Anhui/06-26-YHZGS006-O/2021(AH06) shared low homology with those of the other four H10N3 isolates, with genetic identities <97.04%. Phylogenetic analyses showed that the HA and NA genes of the six H10N3 isolates and human H10N3 strain fell within the Eurasian lineage, and their internal genes were derived from the AIV of the H9N2 subtype. The eight segments of AH06 were placed in the same branch with the human-infecting H10N3 strain, while the PA gene of other isolates was grouped with humaninfecting H3N8 and H9N2 AIVs: the MP gene was more closely related to human-infecting H9N2 AIVs.Molecular characterization showed that all six H10N3 AIV strains had mammalian adaptive mutations such as G228S, which could improve the binding ability to human-type receptors. In summary, we showed the:(i) persistent prevalence of diverse avian H10N3 viruses;(ii) novel human-infecting H10N3 reassortants might have been circulating in poultry in China, and highlighted that they possessed multiple mammalian adaptive mutations. This study provided a theoretical basis for assessment of the public-health risk of H10N3 AIV.
[1] Wu Y, Wu Y, Tefsen B, et al. Bat-derived influenzalike viruses H17N10 and H18N11[J]. Trends Microbiol, 2014, 22(4):183-191. DOI:10. 1016/j.tim. 2014. 01. 010.
[2] Feldmann H, Kretzschmar E, Klingeborn B, et al. The structure of serotype H10 hemagglutinin of influenza A virus:Comparison of an apathogenic avian and a mammalian strain pathogenic for mink[J]. Virology,1988, 165(2):428-437. DOI:10. 1016/0042-6822(88)90586-7.
[3] Wu H, Yang F, Liu F, et al. Molecular characterization of H10 subtype avian influenza viruses isolated from poultry in Eastern China[J]. Arch Virol,2019, 164(1):159-179. DOI:10. 1007/s00705-018-4019-z.
[4] Klingeborn B, Englund L, Rott R, et al. An avian influenza A virus killing a mammalian species—the mink[J]. Arch Virol, 1985, 86(3):347-351. DOI:10. 1007/BF01309839.
[5] Wang N, Zou W, Yang Y, et al. Complete genome sequence of an H10N5 avian influenza virus isolated from pigs in Central China[J]. J Virol, 2012, 86(24):13865-13866. DOI:10. 1128/jvi. 02687-12.
[6] Su S, Qi W, Zhou P, et al. First evidence of H10N8avian influenza virus infections among feral dogs in live poultry markets in Guangdong Province, China[J]. Clin Infect Dis, 2014, 59(5):748-750. DOI:10. 1093/cid/ciu345.
[7] Bodewes R, Bestebroer TM, van der Vries E, et al.Avian Influenza a(H10N7)virus-associated mass deaths among harbor seals[J]. Emerg Infect Dis, 2015, 21(4):720-722. DOI:10. 3201/eid2104. 141675.
[8]袁世超，张宏斌，焦培荣，等.人感染禽流感病毒病例在我国的分布情况[J].中国人兽共患病学报，2022,38(4):374-377. DOI:10. 3969/j. issn. 1002-2694. 2022. 00. 042.
[9]王慎骄，祁贤，余慧燕，等.人感染新型H10N3禽流感病毒分子溯源[J].微生物学通报，2023, 50(3):1231-1244. DOI:10. 13344/j. microbiol. china. 220518.
[10]Qi X, Qiu H, Hao S, et al. Human infection with an avian-origin influenza A(H10N3)virus[J]. N Engl J Med, 2022, 386(11):1087-1088. DOI:10. 1056/nejmc2112416.
[11]Ou X, Chen F, Zhang R, et al. Analysis of the fulllength genome of a novel strain of the H7N9 avian influenza virus[J]. Exp Ther Med, 2014, 7(5):1369-1375. DOI:10. 3892/etm. 2014. 1590.
[12]Kumar S, Stecher G, Li M, et al. MEGA X:molecular evolutionary genetics analysis across computing platforms[J]. Mol Biol Evol, 2018, 35(6):1547-1549. DOI:10. 1093/molbev/msy096.
[13]Katoh K, Standley DM. MAFFT multiple sequence alignment software version 7:improvements in performance and usability[J]. Mol Biol Evol, 2013, 30(4):772-780. DOI:10. 1093/molbev/mst010.
[14]Stamatakis A. RAxML version 8:a tool for phylogenetic analysis and post-analysis of large phylogenies[J]. Bioinformatics, 2014, 30(9):1312-1313. DOI:10. 1093/bioinformatics/btu033.
[15]Portugal JS, Allerdice M, Moraru GM, et al.Molecular phylogeny of Dermacentor parumapertus(Acari:Ixodidae)from two locations within its geographical range[J]. J Med Entomol, 2019, 56(4):979-983. DOI:10. 1093/jme/tjz042.
[16]Liu K, Qi X, Bao C, et al. Novel H10N3 avian influenza viruses:a potential threat to public health[J].Lancet Microbe, 2024, 5(5):e417. DOI:10. 1016/s2666-5247(23)00409-3.
[17]Nu?ez IA, Ross TM. A review of H5Nx avian influenza viruses[J]. Ther Adv Vaccines Immunother,2019, 7:2515135518821625. DOI:10. 1177/2515135518821625.
[18]To KKW, Tsang AKL, Chan JFW, et al. Emergence in China of human disease due to avian influenza a(H10N8)–Cause for concern?[J]. J Infect, 2014, 68(3):205-215. DOI:10. 1016/j. jinf. 2013. 12. 014.
[19]Herfst S, Zhang J, Richard M, et al. Hemagglutinin traits determine transmission of avian A/H10N7influenza virus between mammals[J]. Cell Host Microbe, 2020, 28(4):602-613. e7. DOI:10. 1016/j.chom. 2020. 08. 011.
[20]Nilsson BE, Te Velthuis AJW, Fodor E. Role of the PB2 627 domain in influenza A virus polymerase function[J]. J Virol, 2017, 91(7):e02467-16. DOI:10. 1128/jvi. 02467-16.
[21]Xiao C, Ma W, Sun N, et al. PB2-588 V promotes the mammalian adaptation of H10N8, H7N9 and H9N2avian influenza viruses[J]. Sci Rep, 2016, 6:19474.DOI:10. 1038/srep19474.
[22]Gao W, Zu Z, Liu J, et al. Prevailing I292V PB2mutation in avian influenza H9N2 virus increases viral polymerase function and attenuates IFN-β induction in human cells[J]. J Gen Virol, 2019, 100(9):1273-1281. DOI:10. 1099/jgv. 0. 001294.
[23]Guo Y, Ding P, Li Y, et al. Genetic and biological properties of H10N3 avian influenza viruses:a potential pandemic candidate?[J]. Transbound Emerg Dis,2022, 69(5):e3171-e3182. DOI:10. 1111/tbed. 14458.
[24]Hu M, Chu H, Zhang K, et al. Amino acid substitutions V63I or A37S/I61T/V63I/V100A in the PA N-terminal domain increase the virulence of H7N7influenza A virus[J]. Sci Rep, 2016, 6:37800. DOI:10. 1038/srep37800.
[25]Xu G, Zhang X, Gao W, et al. Prevailing PA mutation K356R in avian influenza H9N2 virus increases mammalian replication and pathogenicity[J]. J Virol,2016, 90(18):8105-8114. DOI:10. 1128/jvi. 00883-16.
[26]Lazniewski M, Dawson WK, Szczepinska T, et al.The structural variability of the influenza A hemagglutinin receptor-binding site[J]. Brief Funct Genomics, 2018, 17(6):415-427. DOI:10. 1093/bfgp/elx042.
[27]Si YJ, Park YR, Baek YG, et al. Pathogenesis and genetic characteristics of low pathogenic avian influenza H10 viruses isolated from migratory birds in South Korea during 2010-2019[J]. Transbound Emerg Dis,2022, 69(5):2588-2599. DOI:10. 1111/tbed. 14409.
[28]Gao R, Zheng H, Liu K, et al. Genesis, evolution and host species distribution of influenza A(H10N3)virus in China[J]. J Infect, 2021, 83(5):607-635. DOI:10. 1016/j. jinf. 2021. 08. 021.
[29]He CQ, Xie ZX, Han GZ, et al. Homologous recombination as an evolutionary force in the avian influenza A virus[J]. Mol Biol Evol, 2009, 26(1):177-187. DOI:10. 1093/molbev/msn238.
[30]Bi Y, Li J, Li S, et al. Dominant subtype switch in avian influenza viruses during 2016–2019 in China[J].Nat Commun, 2020, 11:5909. DOI:10. 1038/s41467-020-19671-3.
[31]Liu D, Shi W, Gao GF. Poultry carrying H9N2 act as incubators for novel human avian influenza viruses[J].Lancet, 2014, 383(9920):869. DOI:10. 1016/s0140-6736(14)60386-x.
[32]Yang ZF, Mok CK, Peiris JS, et al. Human infection with a novel avian influenza a(H5N6)virus[J]. N Engl J Med, 2015, 373(5):487-489. DOI:10. 1056/nejmc1502983.
[33]Xu Q, Jiang F. CT of human infection with avian-origin influenza A(H10N3)virus[J]. Radiology, 2022, 304(3):531. DOI:10. 1148/radiol. 211875.
[34]Zhang M, Zhang X, Xu K, et al. Characterization of the pathogenesis of H10N3, H10N7, and H10N8subtype avian influenza viruses circulating in ducks[J].Sci Rep, 2016, 6:34489. DOI:10. 1038/srep34489.
[35]Zhang Y, Shi J, Cui P, et al. Genetic analysis and biological characterization of H10N3 influenza A viruses isolated in China from 2014 to 2021[J]. J Med Virol,2023, 95(2):e28476. DOI:10. 1002/jmv. 28476.
[36]Liu K, Ding P, Pei Y, et al. Emergence of a novel reassortant avian influenza virus(H10N3)in Eastern China with high pathogenicity and respiratory droplet transmissibility to mammals[J]. Sci China Life Sci,2022, 65(5):1024-1035. DOI:10. 1007/s11427-020-1981-5.
[37]Nicholls JM, Chan RWY, Russell RJ, et al. Evolving complexities of influenza virus and its receptors[J].Trends Microbiol, 2008, 16(4):149-157. DOI:10. 1016/j. tim. 2008. 01. 008.
[38]Gao Y, Zhang Y, Shinya K, et al. Identification of amino acids in HA and PB2 critical for the transmission of H5N1 avian influenza viruses in a mammalian host[J/OL]. PLoS Pathog, 2009, 5(12):e1000709. DOI:10. 1371/journal. ppat. 1000709.
基本信息:
DOI：10.13242/j.cnki.bingduxuebao.004578
中图分类号:R373.1
引用信息:
[1]李珊,董卉,姚雪等.H10N3禽流感病毒安徽分离株遗传多样性研究[J].病毒学报,2024,40(05):1022-1032.DOI:10.13242/j.cnki.bingduxuebao.004578.
基金信息:
泰山学者青年专家计划项目（项目号：tsqn202211217）; 山东第一医科大学“学术提升计划”项目（项目号：2019QL006）~~