中国H9N2亚型禽流感病毒的流行现状

doi:10.11843/j.issn.0366-6964.2021.05.008

摘要/Abstract

摘要： H9N2亚型禽流感病毒（AIVs）持续暴发和流行，不但给养禽业造成了重大损失，而且给公共卫生安全带来了潜在威胁。为了解中国H9N2 AIVs的流行现状，作者对H9N2亚型AIVs的抗原性、受体结合特性、致病性进行了总结，并且对2016—2020年的流行毒株进行了分析。结果显示，H9N2 AIVs在20多个省市地区流行，其中江西、广东、贵州、江苏等地区暴发次数较多。H9N2 AIVs主要感染鸡，少数感染水禽和小家禽，零星感染人。H9N2 AIVs主要位于h9.4.2.5分支，极少数毒株隶属h9.4.2.1分支。当前H9N2 AIVs受体的结合特性呈现双嗜性或优先结合α-2，6 SA受体。抗原相关位点处的氨基酸呈现出多态性，抗原性正在发生着改变。PB2、PA和HA蛋白获得了一些适应性突变，增强了其在哺乳动物细胞上的复制能力以及对小鼠的致病性，增加了其跨宿主传播感染哺乳动物甚者人的风险。综上所述，人们要加强对H9N2 AIVs流行情况的监测，密切关注其抗原特性及致病性的变化。

关键词: H9N2亚型禽流感病毒, 遗传演化, 受体结合特性, 致病性, 抗原性

Abstract: Outbreaks and circulation of H9N2 avian influenza viruses (AIVs) not only cause huge economic losses to poultry industry but also pose a potential threat to public health. In order to illustrate the current epidemiology of H9N2 AIVs in China, their antigenicity, receptor-binding feature and pathogenicity were summarized and viruses that circulated in 2016-2020 were analyzed. The results showed that H9N2 AIVs circulated in more than 20 provinces or cities of China, of which outbreaks occurred more in Jiangxi, Guangdong, Guizhou and Jiangsu. H9N2 AIVs were mainly isolated from chickens, and a few were isolated form waterfowl or small poultry. H9N2 AIVs were sporadically isolated from humans. Most of H9N2 AIVs fell into the clade of h9.4.2.5, and a few isolates belonged to the clade of h9.4.2.1. Current H9N2 AIVs exhibit dual receptor-binding tropism or preferentially binding to α-2-6 SA receptors. The amino acids at the antigen-related sites are polymorphic and the antigenicity is undergoing changes. Some adaptation mutations in PB2, PA and HA protein which enhancing viruses’ replication in mammalian cells and their pathogenicity to mice, were acquired, and those increased the risk of viruses to break through species-barriers to infect other mammals including human. Taken together, the surveillance of H9N2 AIVs and monitoring their variation of antigenicity and pathogenicity should be strengthened.

Key words: H9N2 AIV, evolution, receptor, pathogenicity, antigenicity

中图分类号:

S852.659.5

孙华鹏, 崔新鑫, 潘亮奇, 许丰祥, 李硕, 吴梅花, 朱旭辉, 于亚南, 李明亮, 刘杨, 瞿孝云, 廖明, 孙海亮. 中国H9N2亚型禽流感病毒的流行现状[J]. 畜牧兽医学报, 2021, 52(5): 1218-1229.

SUN Huapeng, CUI Xinxin, PAN Liangqi, XU Fengxiang, LI Shuo, WU Meihua, ZHU Xuhui, YU Yanan, LI Mingliang, LIU Yang, QU Xiaoyun, LIAO Ming, SUN Hailiang. The Epidemiology of H9N2 Avian Influenza Virus in China[J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(5): 1218-1229.

参考文献 68

[1]	陈伯伦, 张泽纪, 陈伟斌. 禽流感研究I. 鸡A型禽流感病毒的分离与血清学初步鉴定[J]. 中国兽医杂志, 1994, 20(10):3-5.CHEN B L, ZHANG Z J, CHEN W B. Avian influenza research I. Isolation and serological preliminary identification of avian influenza A virus[J]. Chinese Journal of Veterinary Medicine, 1994, 20(10):3-5. (in Chinese)
[2]	SUN Y P, LIU J H. H9N2 influenza virus in China:a cause of concern[J]. Protein Cell, 2015, 6(1):18-25.
[3]	PAN Q, LIU A J, ZHANG F M, et al. Co-infection of broilers with Ornithobacterium rhinotracheale and H9N2 avian influenza virus[J]. BMC Vet Res, 2012, 8:104.
[4]	PEIRIS J S M, GUAN Y, MARKWELL D, et al. Cocirculation of avian H9N2 and contemporary “human” H3 N2 influenza A viruses in pigs in southeastern China:potential for genetic reassortment?[J]. J Virol, 2001, 75(20):9679-9686.
[5]	XU C T, FAN W X, WEI R, et al. Isolation and identification of swine influenza recombinant A/Swine/Shandong/1/2003(H9N2) virus[J]. Microbes Infect, 2004, 6(10):919-925.
[6]	CONG Y L, WANG C F, YAN C M, et al. Swine infection with H9N2 influenza viruses in China in 2004[J]. Virus Genes, 2008, 36(3):461-469.
[7]	CONG Y L, PU J, LIU Q F, et al. Antigenic and genetic characterization of H9N2 swine influenza viruses in China[J]. J Gen Virol, 2007, 88(Pt 7):2035-2041.
[8]	PEIRIS M, YUEN K Y, LEUNG C W, et al. Human infection with influenza H9N2[J]. Lancet, 1999, 354(9182):916-917.
[9]	PAN Y, CUI S, SUN Y, et al. Human infection with H9N2 avian influenza in northern China[J]. Clin Microbiol Infect, 2018, 24(3):321-323.
[10]	HE J, WU Q, YU J L, et al. Sporadic occurrence of H9N2 avian influenza infections in human in Anhui province, eastern China:A notable problem[J]. Microb Pathog, 2020, 140:103940.
[11]	HUANG Y W, LI X D, ZHANG H, et al. Human infection with an avian influenza A (H9N2) virus in the middle region of China[J]. J Med Virol, 2015, 87(10):1641-1648.
[12]	ZHOU P, ZHU W J, GU H L, et al. Avian influenza H9N2 seroprevalence among swine farm residents in China[J]. J Med Virol, 2014, 86(4):597-600.
[13]	WANG Q, JU L, LIU P, et al. Serological and virological surveillance of avian influenza A virus H9N2 subtype in humans and poultry in Shanghai, China, between 2008 and 2010[J]. Zoonoses Public Health, 2015, 62(2):131-140.
[14]	YU Q, LIU L Q, PU J, et al. Risk perceptions for avian influenza virus infection among poultry workers, China[J]. Emerg Infect Dis, 2013, 19(2):313-316.
[15]	HUANG R, WANG A R, LIU Z H, et al. Seroprevalence of avian influenza H9N2 among poultry workers in Shandong Province, China[J]. Eur J Clin Microbiol Infect Dis, 2013, 32(10):1347-1351.
[16]	GAO R B, CAO B, HU Y W, et al. Human infection with a novel avian-origin influenza A (H7 N9) virus[J]. N Engl J Med, 2013, 368(20):1888-1897.
[17]	CHEN H Y, YUAN H, GAO R B, et al. Clinical and epidemiological characteristics of a fatal case of avian influenza A H10N8 virus infection:a descriptive study[J]. Lancet, 2014, 383(9918):714-721.
[18]	DALBY A R, IQBAL M. A global phylogenetic analysis in order to determine the host species and geography dependent features present in the evolution of avian H9N2 influenza hemagglutinin[J]. PeerJ, 2014, 2:e655.
[19]	GU M, XU L J, WANG X Q, et al. Current situation of H9N2 subtype avian influenza in China[J]. Vet Res, 2017, 48(1):49.
[20]	JIN Y, YU D, REN H G, et al. Phylogeography of Avian influenza A H9N2 in China[J]. BMC Genomics, 2014, 15(1):1110.
[21]	JIANG W M, LIU S, HOU G Y, et al. Chinese and global distribution of H9 subtype avian influenza viruses[J]. PLoS One, 2012, 7(12):e52671.
[22]	XU K M, LI K S, SMITH G J D, et al. Evolution and molecular epidemiology of H9N2 influenza A viruses from quail in southern China, 2000 to 2005[J]. J Virol, 2007, 81(6):2635-2645.
[23]	SUN Y P, PU J, JIANG Z L, et al. Genotypic evolution and antigenic drift of H9N2 influenza viruses in China from 1994 to 2008[J]. Vet Microbiol, 2010, 146(3-4):215-225.
[24]	LI C, WANG S G, BING G X, et al. Genetic evolution of influenza H9N2 viruses isolated from various hosts in China from 1994 to 2013[J]. Emerg Microbes Infect, 2017, 6(11):e106.
[25]	段旭彤. H9N2亚型禽流感病毒HA蛋白的抗原变异及受体结合特性分析[D]. 哈尔滨:黑龙江大学, 2017.DUAN X T. Analysis of antigenic variation and receptor binding characteristics of HA protein of H9N2 subtype avian influenza virus[D]. Harbin:Heilongjiang University, 2017. (in Chinese)
[26]	SANG X Y, WANG A R, DING J, et al. Adaptation of H9N2 AIV in guinea pigs enables efficient transmission by direct contact and inefficient transmission by respiratory droplets[J]. Sci Rep, 2015, 5:15928.
[27]	TENG Q Y, XU D W, SHEN W X, et al. A single mutation at position 190 in hemagglutinin enhances binding affinity for human type sialic acid receptor and replication of H9N2 avian influenza virus in mice[J]. J Virol, 2016, 90(21):9806-9825.
[28]	LI X Y, SHI J Z, GUO J, et al. Genetics, receptor binding property, and transmissibility in mammals of naturally isolated H9N2 avian influenza viruses[J]. PLoS Pathog, 2014, 10(11):e1004508.
[29]	YUAN J, XU L L, BAO L L, et al. Characterization of an H9N2 avian influenza virus from a Fringilla montifringilla brambling in northern China[J]. Virology, 2015, 476:289-297.
[30]	ZOU S M, ZHANG Y, LI X Y, et al. Molecular characterization and receptor binding specificity of H9N2 avian influenza viruses based on poultry-related environmental surveillance in China between 2013 and 2016[J]. Virology, 2019, 529:135-143.
[31]	WANG D D, WANG J J, BI Y H, et al. Characterization of avian influenza H9N2 viruses isolated from ostriches (Struthio camelus)[J]. Sci Rep, 2018, 8(1):2273.
[32]	SUN H L, LIN J T, LIU Z T, et al. Genetic, molecular, and pathogenic characterization of the H9N2 avian influenza viruses currently circulating in South China[J]. Viruses, 2019, 11(11):1040.
[33]	SANG X Y, WANG A R, CHAI T J, et al. Rapid emergence of a PB2-E627K substitution confers a virulent phenotype to an H9N2 avian influenza virus during adaption in mice[J]. Arch Virol, 2015, 160(5):1267-1277.
[34]	SEALY J E, YAQUB T, PEACOCK T P, et al. Association of increased receptor-binding avidity of influenza A(H9N2) viruses with escape from antibody-based immunity and enhanced zoonotic potential[J]. Emerg Infect Dis, 2018, 25(1):63-72.
[35]	PEACOCK T P, BENTON D J, JAMES J, et al. Immune escape variants of H9N2 influenza viruses containing deletions at the hemagglutinin receptor binding site retain fitness in vivo and display enhanced zoonotic characteristics[J]. J Virol, 2017, 91(14):e00218-17.
[36]	WAN H Q, PEREZ D R. Amino acid 226 in the hemagglutinin of H9N2 influenza viruses determines cell tropism and replication in human airway epithelial cells[J]. J Virol, 2007, 81(10):5181-5191.
[37]	PEACOCK T P, BENTON D J, SADEYEN J R, et al. Variability in H9N2 haemagglutinin receptor-binding preference and the pH of fusion[J]. Emerg Microbes Infect, 2017, 6(1):1-7.
[38]	XU Y, PENG R C, ZHANG W, et al. Avian-to-human receptor-binding adaptation of avian H7 N9 influenza virus hemagglutinin[J]. Cell Rep, 2019, 29(8):2217-2228.E5.
[39]	LI C J, YU K Z, TIAN G B, et al. Evolution of H9N2 influenza viruses from domestic poultry in Mainland China[J]. Virology, 2005, 340(1):70-83.
[40]	ZHANG Y, YIN Y B, BI Y H, et al. Molecular and antigenic characterization of H9N2 avian influenza virus isolates from chicken flocks between 1998 and 2007 in China[J]. Vet Microbiol, 2012, 156(3-4):285-293.
[41]	ZHAO Y X, LI S, ZHOU Y F, et al. Phylogenetic analysis of hemagglutinin genes of H9N2 avian influenza viruses isolated from chickens in Shandong, China, between 1998 and 2013[J]. BioMed Res Int, 2015, 2015:267520.
[42]	GE F F, LI X, JU H B, et al. Genotypic evolution and antigenicity of H9N2 influenza viruses in Shanghai, China[J]. Arch Virol, 2016, 161(6):1437-1445.
[43]	ZHU R, XU D W, YANG X Q, et al. Genetic and biological characterization of H9N2 avian influenza viruses isolated in China from 2011 to 2014[J]. PLoS One, 2018, 13(7):e0199260.
[44]	XIA J, CUI J Q, HE X, et al. Genetic and antigenic evolution of H9N2 subtype avian influenza virus in domestic chickens in southwestern China, 2013-2016[J]. PLoS One, 2017, 12(2):e0171564.
[45]	LI Y, LIU M D, SUN Q Q, et al. Genotypic evolution and epidemiological characteristics of H9N2 influenza virus in Shandong Province, China[J]. Poult Sci, 2019, 98(9):3488-3495.
[46]	KAVERIN N V, RUDNEVA I A, ILYUSHINA N A, et al. Structural differences among hemagglutinins of influenza A virus subtypes are reflected in their antigenic architecture:Analysis of H9 escape mutants[J]. J Virol, 2004, 78(1):240-249.
[47]	WAN Z M, YE J Q, XU L L, et al. Antigenic mapping of the hemagglutinin of an H9N2 avian influenza virus reveals novel critical amino acid positions in antigenic sites[J]. J Virol, 2014, 88(7):3898-3901.
[48]	PENG Q Q, ZHU R, WANG X B, et al. Impact of the variations in potential glycosylation sites of the hemagglutinin of H9N2 influenza virus[J]. Virus Genes, 2019, 55(2):182-190.
[49]	JIN F, DONG X M, WAN Z M, et al. A single mutation N166D in hemagglutinin affects antigenicity and pathogenesis of H9N2 avian influenza virus[J]. Viruses, 2019, 11(8):709.
[50]	SONG J W, WANG C X, GAO W H, et al. A D200 N hemagglutinin substitution contributes to antigenic changes and increased replication of avian H9N2 influenza virus[J]. Vet Microbiol, 2020, 245:108669.
[51]	ZHU Y B, YANG D, REN Q, et al. Identification and characterization of a novel antigenic epitope in the hemagglutinin of the escape mutants of H9N2 avian influenza viruses[J]. Vet Microbiol, 2015, 178(1-2):144-149.
[52]	IQBAL M, YAQUB T, REDDY K, et al. Novel genotypes of H9N2 influenza A viruses isolated from poultry in Pakistan containing NS genes similar to highly pathogenic H7N3 and H5N1 viruses[J]. PLoS One, 2009, 4(6):e5788.
[53]	OKAMATSU M, SAKODA Y, KISHIDA N, et al. Antigenic structure of the hemagglutinin of H9N2 influenza viruses[J]. Arch Virol, 2008, 153(12):2189-2195.
[54]	PEACOCK T, REDDY K, JAMES J, et al. Antigenic mapping of an H9N2 avian influenza virus reveals two discrete antigenic sites and a novel mechanism of immune escape[J]. Sci Rep, 2016, 6:18745.
[55]	SHI H Y, ASHRAF S, GAO S, et al. Evaluation of transmission route and replication efficiency of H9N2 avian influenza virus[J]. Avian Dis, 2010, 54(1):22-27.
[56]	李凤艳. 4株H9N2亚型禽流感病毒分离株对SPF鸡致病性研究[J]. 现代畜牧兽医, 2017(9):9-12.LI F Y. Pathogenicity of 4 strains of H9N2 subtype avian influenza virus to SPF chickens[J]. Modern Journal of Animal Husbandry and Veterinary Medicine, 2017(9):9-12. (in Chinese)
[57]	冯贺龙, 任助, 焦哲, 等. 2株H9N2亚型禽流感病毒对鹌鹑的致病性[J]. 中国兽医学报, 2020, 40(3):547-551.FENG H L, REN Z, JIAO Z, et al. Pathogenicity study of 2 H9N2 avian influenza viruses for quails[J]. Chinese Journal of Veterinary Science, 2020, 40(3):547-551. (in Chinese)
[58]	SONG Y F, ZHANG Y, CHEN L, et al. Genetic characteristics and pathogenicity analysis in chickens and mice of three H9N2 avian influenza viruses[J]. Viruses, 2019, 11(12):1127.
[59]	YE G, LIANG C H, HUA D G, et al. Phylogenetic analysis and pathogenicity assessment of two strains of avian influenza virus subtype H9N2 isolated from migratory birds:high homology of internal genes with human H10N8 virus[J]. Front Microbiol, 2016, 7:57.
[60]	CHEN Z K, HUANG Q H, YANG S H, et al. A well-defined H9N2 avian influenza virus genotype with high adaption in mammals was prevalent in Chinese poultry between 2016 to 2019[J]. Viruses, 2020, 12(4):432.
[61]	KAMIKI H, MATSUGO H, KOBAYASHI T, et al. A PB1-K577E mutation in H9N2 influenza virus increases polymerase activity and pathogenicity in mice[J]. Viruses, 2018, 10(11):653.
[62]	GAO W H, ZU Z P, LIU J Y, et al. Prevailing I292V PB2 mutation 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.
[63]	ZHANG J F, SU R, JIAN X Y, et al. The D253 N mutation in the polymerase basic 2 gene in avian influenza (H9N2) virus contributes to the pathogenesis of the virus in mammalian hosts[J]. Virol Sin, 2018, 33(6):531-537.
[64]	WANG C R, LEE H H Y, YANG Z F, et al. PB2-Q591K mutation determines the pathogenicity of avian H9N2 influenza viruses for mammalian species[J]. PLoS One, 2016, 11(9):e0162163.
[65]	WANG C X, WANG Z J, REN X L, et al. Infection of chicken H9N2 influenza viruses in different species of domestic ducks[J]. Vet Microbiol, 2019, 233:1-4.
[66]	钟芝兰, 张增峰. 鸭源H9N2 AIV在人肺组织的复制研究[J]. 畜牧兽医科学(电子版), 2020(10):7-9.ZHONG Z L, ZHANG Z F. Replication of duck-derived H9N2 AIV in human lung tissue[J]. Graziery Veterinary Sciences (Electronic Version), 2020(10):7-9. (in Chinese)
[67]	XU G L, ZHANG X X, GAO W H, et al. Prevailing PA mutation K356R in avian influenza H9N2 virus increases mammalian replication and pathogenicity[J]. J Virol, 2016, 90(18):8105-8114.
[68]	WANG J J, SUN Y P, XU Q, et al. Mouse-adapted H9N2 influenza A virus PB2 protein M147L and E627K mutations are critical for high virulence[J]. PLoS One, 2012, 7(7):e40752.