| 360 | 2 | 99 |
| 下载次数 | 被引频次 | 阅读次数 |
2017年夏季,我国广东及香港地区H3N2亚型流感病毒暴发流行,造成至少430人死亡。为揭示其流行原因,本研究对广东及中国香港地区2016和2017年夏季流行的甲型H3N2流感病毒血凝素(Hemagglutinin,HA)和神经氨酸酶(Neuraminidase,NA)基因的分子遗传特征进行了分析。采集深圳市2017年夏季流感样症状患者的样本进行H3N2病毒的检测及分离鉴定。利用逆转录-聚合酶链反应(Reverse transcription-polymerase chain reaction,RTPCR)扩增病毒HA、NA基因并测序,用于进一步分析;从流感病毒数据库中下载广东及中国香港地区同期流行的H3N2代表毒株进行遗传变异分析。HA基因系统进化分析显示:广东及中国香港地区2016～2017年流行的H3N2病毒与疫苗株均处于同一进化分支,其中2016年流行毒株与疫苗株的同源性(99.1%～99.4%)高于2017年流行毒株(98.3%～99.4%)。HA蛋白氨基酸分析结果显示,广东及中国香港地区2017年流行株在抗原位点A区158和160位氨基酸、受体结合区域的130-loop和220-loop、以及151位糖基化位点与疫苗株相比出现了较高比例突变,而在2016年流行毒株中没有发现。同时,这些位点在中国香港地区流行毒株中的突变频率高于广东地区流行毒株。NA蛋白氨基酸分析显示,所有毒株均未发现神经氨酸酶抑制剂耐药突变,中国香港地区2017年部分流行毒株234位和329位氨基酸糖基化位点消失(比例分别为12.6%和54.8%)。尽管2016年和2017年H3N2疫苗株为同一株病毒,但是2017年广东和中国香港地区的H3N2病毒流行毒株与2016年流行毒株以及疫苗株相比,在HA蛋白的主要抗原位点和受体结合位点均出现不同程度的变异,推测本次H3N2流感病毒暴发流行可能与这些变异相关。
Abstract：An outbreak of infection by influenza A virus H3N2 in Guangdong province and Hong Kong,China,in the summer of 2017 caused over 430 deaths. To explore the possible reasons for its prevalence,we analyzed the molecular and genetic characteristics of the hemagglutinin(HA)and neuraminidase(NA)genes of H3 N2 viruses from Guangdong Province,China and Hong Kong,China in 2016 and 2017. Samples from patients with influenza-like symptoms in Shenzhen,China,were collected in the summer of 2017,and H3N2 virus was detected and isolated. HA and NA genes of the virus were amplified by reverse transcription-polymerase chain reaction(RT-PCR)for further analysis. The sequences of H3N2 strains from Guangdong Province,China and Hong Kong,China were downloaded from the influenza databases. Phylogenetic analysis of the HA genes showed that there were some evolutionary distances between the vaccine strain and the strains from Guangdong Province,China and Hong Kong,China even though they were clustered in the main branch,while the nucleotide identity was higher for the strains in 2016(99.1%-99.4%)than those in 2017(98.3%-99.4%).Compared with the vaccine strain,the HA protein of strains from Guangdong Province,China and Hong Kong,China in 2017 possessed a high mutation rate at amino acids 158 and 160 in the antigenic site A,the 130-loop and 220-loop of the receptor binding region and the glycosylation site 151,but not in strains from 2016.Additionally,a higher mutation rate was observed in strains from Hong Kong,China. Neuraminidase inhibitorresistant mutations were not found,while some strains from Hong Kong,China,in 2017 lost the glycosylation sites 234 and 329(the proportions were 12.6% and 54.8%,respectively). In conclusion,although the recommended vaccine strains were same in 2016 and 2017,the prevalent H3 N2 viruses from Guangdong Province,China and Hong Kong,China,in 2017 possessed a higher proportions of variation in the main antigenic site and the receptor binding domain of HA protein,which may have contributed to the outbreak of infection by influenza A virus H3 N2 in 2017.
[1]Gao G F.From“A”IV to“Z”IKV:attacks from emerging and re-emerging pathogens[J].Cell,2018,172(6):1157-1159.
[2]Long J S,Mistry B,Haslam S M,Barclay W S.Host and viral determinants of influenza A virus species specificity[J].Nat Rev Microbiol,2019,17(2):67-81.
[3]Krammer F,Smith G J D,Fouchier R A M,Peiris M,Kedzierska K,Doherty P C,Palese P,Shaw M L,Treanor J,Webster R G,García-Sastre A.Influenza[J/OL].Nat Rev Dis Primers,2018,4(1):3.DOI:10.1038/s41572-018-0002-y.
[4]Gaymard A,Le Briand N,Frobert E,Lina B,Escuret V.Functional balance between neuraminidase and hemagglutinin in influenza viruses[J].Clin Microbiol Infect,2016,22(12):975-983.
[5]Bi Y,Xiao H,Chen Q,Wu Y,Fu L,Quan C,Wong G,Liu J,Haywood J,Liu Y,Zhou B,Yan J,Liu W,Gao G F.Changes in the length of the neuraminidase stalk region impacts H7N9 virulence in mice[J].JVirol,2015,90(4):2142-2149.
[6]Gen F,Yamada S,Kato K,Akashi H,Kawaoka Y,Horimoto T.Attenuation of an influenza A virus due to alteration of its hemagglutinin-neuraminidase functional balance in mice[J].Arch Virol,2013,158(5):1003-1011.
[7]Xu R,Zhu X,Mcbride R,Nycholat C M,Yu W,Paulson J C,Wilson I A.Functional balance of the hemagglutinin and neuraminidase activities accompanies the emergence of the 2009 H1N1 influenza pandemic[J].J Virol,2012,86(17):9221-9232.
[8]吴衍恒，欧慧，师舞阳，谢颖，周日东.2010-2013年中山市流感病毒(H3N2)血凝素基因特征分析[J].实用预防医学，2015,22(4):420-423.
[9]De Donno A,Idolo A,Quattrocchi M,Zizza A,Gabutti G,Romano A,Grima P,Donatelli I,Guido M.Surveillance of human influenza A(H3N2) virus from 1999 to 2009 in southern Italy[J].Epidemiol Infect,2014,142(5):933-939.
[10]Weis W,Brown J H,Cusack S,Paulson J C,Skehel JJ,Wiley D C.Structure of the influenza virus haemagglutinin complexed with its receptor,sialic acid[J].Nature,1988,333(6172):426-431.
[11]Mcclellan K.Oseltamivir[J].Drugs,2001,61(2):263-283.
[12]Abed Y,Boivin G.A review of clinical influenza A and B infections with reduced susceptibility to both oseltamivir and zanamivir[J/OL].Open Forum Infect Dis,2017,4(3):105.DOI:10.1093/ofid/ofx105.
[13]黄维娟，谭敏菊，李希妍，成艳辉，隗合江，肖宁，赵翔，曾晓旭，王大燕.2013~2017年中国大陆流行的A(H3N2)亚型流感病毒对神经氨酸酶抑制剂的敏感性分析[J].病毒学报，2018,34(6):793-798.DOI:10.13242/j.cnki.bingduxuebao.003465.
[14]Allen J D,Ross T M.H3N2 influenza viruses in humans:viral mechanisms,evolution,and evaluation[J].Hum Vaccin Immunother,2018,14(8):1840-1847.
[15]Jennings L,Huang Q S,Barr I,Lee P,Kim W J,Buchy P,Sanicas M,Mungall B A,Chen J.Literature review of the epidemiology of influenza B disease in 15countries in the Asia-Pacific region[J].Influenza Other Respir Viruses,2018,12(3):383-411.
[16]广东省卫生健康委员会.省卫生计生委发布季节性流感预警信息[EB/OL].http：//wsjkw.gd.gov.cn/zwyw_yqxx/content/post_1944115.html.
[17]广东省卫生健康委员会.省卫生计生委：我省流感疫情平稳，群众不必恐慌[EB/OL].http：//wsjkw.gd.gov.cn/zwyw_gzdt/content/post_1941718.html.
[18]深圳市疾病预防控制中心.深圳流感仍高发，但活跃水平呈下降趋势[EB/OL].http：//www.szcdc.net/jkdt/zxdt/yqcl/201708/t20170808_8068937.htm.
[19]香港特别行政区政府卫生署卫生防护中心.夏季流感季节完结，市民需持续保持卫生预防感染[EB/OL].https：//sc.isd.gov.hk/Tuni S/www.info.gov.hk/gia/general/201708/30/P2017083000394.htm.
[20]World Health Organization.WHO recommendations on the composition of influenza virus vaccines[EB/OL].https：//www.who.int/influenza/vaccines/virus/recommendations/en/.
[21]Fang Q,Gao Y,Chen M,Guo X,Yang X,Yang X,Wei L.Molecular epidemiology and evolution of A(H1N1)pdm09 and H3N2 virus during winter 2012-2013 in Beijing,China[J].Infect Genet Evol,2014,26:228-240.
[22]Yang H,Carney P J,Chang J C,Guo Z,Villanueva JM,Stevens J.Structure and receptor binding preferences of recombinant human A (H3N2) virus hemagglutinins[J].Virology,2015,477:18-31.
[23]Huang J W,Yang J M.Changed epitopes drive the antigenic drift for influenza A(H3N2)viruses[J/OL].BMC Bioinformatics,2011,12(S1):S31.DOI:10.1186/1471-2105-12-S1-S31.
[24]王勇，薛颖，陈淑霞，金奇，侯云德.H3N2亚型人流行性感冒病毒HA1的蛋白序列同源性比较、变异规律及结构与功能的分析[J].病毒学报，2002,18(4):289-296.DOI:10.3321/j.issn:1000-8721.2002.04.001.
[25]黄平，钟静，梁丽君，侯年妹，倪汉忠，武婕，张欣.广东地区流感H3N2毒株血凝素基因特征、进化和变异分析[J].病毒学报，2012,28(4):330-335.DOI:10.13242/j.cnki.bingduxuebao.002286.
[26]孙海波，刘双，宋亦春，孙柏红，宋歌，王璐璐，孙英伟.辽宁省2016-2017年H3N2亚型流感病毒HA1基因特征分析[J].中国微生态学杂志，2018,30(1):35-38.
[27]Kim P,Jang Y H,Kwon S B,Lee C M,Han G,Seong B L.Glycosylation of hemagglutinin and neuraminidase of influenza A virus as signature for ecological spillover and adaptation among influenza reservoirs[J/OL].Viruses,2018,10(4):183.DOI:10.3390/v10040183.
[28]An Y,Parsons L M,Jankowska E,Melnyk D,Joshi M,Cipollo J F.N-glycosylation of seasonal influenza vaccine hemagglutinins:implication for potency testing and immune processing[J].J Viro,2018,93(2):1693-1718.
[29]Tate M D,Job E R,Deng Y M,Gunalan V,MaurerStroh S,Reading P C.Playing hide and seek:how glycosylation of the influenza virus hemagglutinin can modulate the immune response to infection[J].Viruses,2014,6(3):1294-316.
[30]陈国清，李春香，邵荣标，王瑶，李峰，徐士林，李长城.2015-2017年盐城市甲型H3N2流感病毒HA1、NA基因分子特征[J].中华疾病控制杂志，2018,22(9):36-41.
[31]An Y,Mccullers J A,Alymova I,Parsons L M,Cipollo J F.Glycosylation analysis of engineered H3N2influenza A virus hemagglutinins with sequentially added historically relevant glycosylation sites[J].J Proteome Res,2015,14(9):3957-3969.
[32]EI Moussi A,Ali B H K M,Slim A.Loss and gain of N-linked glycosylation sites in globular head and stem of HA found in A/H3N2 flu fatal and severe cases during2013 Tunisia flu seasonal survey[J].Virus Genes,2014,48(1):189-192.
[33]Su S,Chaves S S,Perez A,D′Mello T,Kirley P D,Yousey-Hindes K,Farley M M,Harris M,Sharangpani R,Lynfield R,Morin C,Hancock E B,Zansky S,Hollick G E,Fowler B,Mc Donald-Hamm C,Thomas A,Horan V,Lindegren M L,Schaffner W,Price A,Bandyopadhyay A,Fry A M.Comparing clinical characteristics between hospitalized adults with laboratory-confirmed influenza A and B virus infection[J].Clin Infect Dis,2014,59(2):252-255.
[34]Domínguez A,Romerotamarit A,Soldevila N,Godoy P,JanéM,Martínez A,Torner N,CaylàJ A,Rius C.Effectiveness of antiviral treatment in preventing death in severe hospitalised influenza cases over six seasons[J].Epidemiol Infect,2018,146(7):799-808.
[35]邢晓会，王大燕，舒跃龙.流行性感冒病毒耐药性监测研究进展[J].中华预防医学杂志，2012,46(5):468-470.
[36]Hussain M,Galvin H D,Haw T Y,Nutsford A N,Husain M.Drug resistance in influenza A virus:the epidemiology and management[J].Infect Drug Resist,2017,10:121-134.
[37]Lackenby A,Besselaar T G,Daniels R S,Fry A,Gregory V,Gubareva L V,Huang W,Hurt A C,Leang S,Lee R T C,Lo J,Lollis L,Maurer-Stroh S,Odagiri T,Pereyaslov D,Takashita E,Wang D,Zhang W,Meijer A.Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors,2016-2017[J].Antiviral Res,2018,157:38-46.
基本信息:
DOI：10.13242/j.cnki.bingduxuebao.003861
中图分类号:R373.13
引用信息:
[1]许智祥,李善琴,沈晨光,等.广东及中国香港地区2016年和2017年甲型H3N2流感病毒的分子特征分析[J].病毒学报,2021,37(01):79-88.DOI:10.13242/j.cnki.bingduxuebao.003861.
基金信息:
“艾滋病和病毒性肝炎等重大传染病防治”科技重大专项(项目号：2018ZX10711001)，题目：病毒感染高通量快速检测与应急筛检技术研究; 深圳市科创委科技研究和发展学科布局项目(项目号：JCYJ20180504165549581)，题目：深圳市禽流感病毒跨种传播风险评估模型的建立及应用研究~~
2021-01-19
2021-01-19
2021-01-19