江浙沪地区EV71的分子流行病学特征
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摘要
目的研究江浙沪地区EV71-VP1遗传变异特征,了解江浙沪地区EV71病毒基因突变及抗原变异规律,为EV71的预防、治疗提供帮助。方法从GenBank上下载了江浙沪地区2009-2014年共79株EV71的VP1区段序列与各亚型参考株序列,用MEGA7.0软件构建进化树,分析江浙沪地区EV71-VP1分子流行病学特征;用疫苗株FY23株做为参考株比较江浙沪地区EV71毒株的氨基酸变异情况。结果通过进化树与序列同源分析,发现79株毒株均为C4a亚型,江浙沪地区EV71毒株可分为两个大簇与数个小簇,两个大簇间没有发现明显的序列差异,江浙沪三个地区的毒株在进化树上的分布不存在明显的差异。79株毒株共存在34个氨基酸位点突变,其中与病毒致病及疫苗接种效果相关的98、145、289位点发生多株突变,7株发生了病毒与受体结合相关的E145G/Q突变,7株发生了位于病毒表面BC环内的E98K突变,5株发生了与临床症状表现相关的A289T/V突变,未发现2009-2014年有明显的EV71毒株氨基酸变异差异。结论虽然2009-2014年江浙沪地区的EV71毒株流行亚型没有改变,也不存在明显地区间的流行差异,但是病毒的基因及氨基酸突变较为多见,仍应关注该地区的病毒基因及抗原变异,以便更好的预防EV71疫情。
OBJECTIVE To investigate the EV71-VP1 gene variation characteristics in Jiangsu,Zhejiang and Shanghai region,and understand the laws of development of gene and antihelion of EV71 virus in Jiangsu,Zhejiang and Shanghai region,so as to give help for the prevention and treatment of EV71 infection.METHODS Reference strains of various subtypes and a total of 79 strains of EV71-VP1 gene sequence of Jiangsu,Zhejiang and Shanghai region between 2009 and 2014 from GenBank were downloaded,the phylogenetic tree was constructed by MEGA7.0software,and molecular epidemiology characteristics of EV71-VP1 in Jiangsu,Zhejiang and Shanghai region were analyzed.FY23 strain was used as the reference strain to analyze mutations of amino acids.RESULTS The phylogenetic tree and sequence homology analysis showed that 79 strains were all C4 asubtypes.The 79 strains of Jiangsu,Zhejiang and Shanghai region could be divided into 2bigger groups and several smaller groups,there were no obvious difference between 2bigger groups in the phylogenetic tree,and the strain distribution in the phylogenetic tree had no obvious difference between Jiangsu,Zhejiang and Shanghai either.Totally 34 mutation sites were found after analyzing amino acids in VP1,while 98,145,and 289 sites had plural mutants,which might be related to the pathogenic factors of the virus and effect of vaccination.Totally 7strains had mutations at145(E145G/Q)associated with the reporter blinding,7strains had mutations at 98(E98K)in the BC loops which was on the surface of the virus particles,and 5strains had mutations at 289(A289T/V)which might be more possible to get severe clinical symptoms.No significant differences in amino acid variation of EV71 strain were found from 2009 to 2014.CONCLUSIONThe subtype of EV71 in Jiangsu,Zhejiang and Shanghai region doesn′t change from 2009 to 2014,and also has no obvious regional differences,but the genes and amino acid mutations are common,so we should keep focusing on the nucleic acid mutation and antigenic variation,in order to prevent the outbreak of EV71.
OBJECTIVE To investigate the EV71-VP1 gene variation characteristics in Jiangsu,Zhejiang and Shanghai region,and understand the laws of development of gene and antihelion of EV71 virus in Jiangsu,Zhejiang and Shanghai region,so as to give help for the prevention and treatment of EV71 infection.METHODS Reference strains of various subtypes and a total of 79 strains of EV71-VP1 gene sequence of Jiangsu,Zhejiang and Shanghai region between 2009 and 2014 from GenBank were downloaded,the phylogenetic tree was constructed by MEGA7.0software,and molecular epidemiology characteristics of EV71-VP1 in Jiangsu,Zhejiang and Shanghai region were analyzed.FY23 strain was used as the reference strain to analyze mutations of amino acids.RESULTS The phylogenetic tree and sequence homology analysis showed that 79 strains were all C4 asubtypes.The 79 strains of Jiangsu,Zhejiang and Shanghai region could be divided into 2bigger groups and several smaller groups,there were no obvious difference between 2bigger groups in the phylogenetic tree,and the strain distribution in the phylogenetic tree had no obvious difference between Jiangsu,Zhejiang and Shanghai either.Totally 34 mutation sites were found after analyzing amino acids in VP1,while 98,145,and 289 sites had plural mutants,which might be related to the pathogenic factors of the virus and effect of vaccination.Totally 7strains had mutations at145(E145G/Q)associated with the reporter blinding,7strains had mutations at 98(E98K)in the BC loops which was on the surface of the virus particles,and 5strains had mutations at 289(A289T/V)which might be more possible to get severe clinical symptoms.No significant differences in amino acid variation of EV71 strain were found from 2009 to 2014.CONCLUSIONThe subtype of EV71 in Jiangsu,Zhejiang and Shanghai region doesn′t change from 2009 to 2014,and also has no obvious regional differences,but the genes and amino acid mutations are common,so we should keep focusing on the nucleic acid mutation and antigenic variation,in order to prevent the outbreak of EV71.
引文
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[4]Wang X,Peng W,Ren J,et al.A sensor-adaptor mechanism for enterovirus uncoating from structures of EV71[J].Nat Struct Mol Biol,2012,19(4):424-429.
[5]Chang GH,Luo YJ,Wu XY,et al.Monoclonal antibody induced with inactived EV71-Hn2virus protects mice against lethal EV71-Hn2virus infection[J].Virol J,2010(7):106.
[6]Nishimura Y,Lee H,Hafenstein S,et al.Enterovirus 71binding to PSGL-1on leukocytes:VP1-145acts as a molecular switch to control receptor interaction[J].PLoS Pathog,2013,9(7):e1003511.
[7]蔡韵,申惠国,李治俊,等.2011年上海地区轻、重症手足口病患者肠道病毒71型分离株VP1、VP4区的基因特征分析[J].中华传染病杂志,2013,31(1):12-18.
[8]吴娴波,钟艳云,曹宇娟,等.广东EV71病毒流行病学特征和毒力分析et al.实用医学杂志,2015(6):999-1002.
[9]Lim XF,Jia Q,Khong WX,et al.Characterization of an isotype-dependent monoclonal antibody against linear neutralizing epitope effective for prophylaxis of enterovirus 71infection[J].PLoS One,2012,7(1):e29751.
[10]Yuan S,Li G,Wang Y,et al.Identification of positively charged residues in enterovirus 71capsid protein VP1essential for production of infectious particles[J].J Virol,2015,90(2):741-752.
[2]Chong P,Liu CC,Chow YH,et al.Review of enterovirus 71vaccines[J].Clin Infect Dis,2015,60(5):797-803.
[3]李静,雷亚克,蒋晓清,等.湖北肠道病毒EV71型流行株VP1基因以及蛋白结构特征分析et al.中国人兽共患病学报,2013,29(11):1099-1104.
[4]Wang X,Peng W,Ren J,et al.A sensor-adaptor mechanism for enterovirus uncoating from structures of EV71[J].Nat Struct Mol Biol,2012,19(4):424-429.
[5]Chang GH,Luo YJ,Wu XY,et al.Monoclonal antibody induced with inactived EV71-Hn2virus protects mice against lethal EV71-Hn2virus infection[J].Virol J,2010(7):106.
[6]Nishimura Y,Lee H,Hafenstein S,et al.Enterovirus 71binding to PSGL-1on leukocytes:VP1-145acts as a molecular switch to control receptor interaction[J].PLoS Pathog,2013,9(7):e1003511.
[7]蔡韵,申惠国,李治俊,等.2011年上海地区轻、重症手足口病患者肠道病毒71型分离株VP1、VP4区的基因特征分析[J].中华传染病杂志,2013,31(1):12-18.
[8]吴娴波,钟艳云,曹宇娟,等.广东EV71病毒流行病学特征和毒力分析et al.实用医学杂志,2015(6):999-1002.
[9]Lim XF,Jia Q,Khong WX,et al.Characterization of an isotype-dependent monoclonal antibody against linear neutralizing epitope effective for prophylaxis of enterovirus 71infection[J].PLoS One,2012,7(1):e29751.
[10]Yuan S,Li G,Wang Y,et al.Identification of positively charged residues in enterovirus 71capsid protein VP1essential for production of infectious particles[J].J Virol,2015,90(2):741-752.