基于全基因组序列对新型H7N9禽流感病毒进化率评估
|
摘要
目的基于新型H7N9禽流感病毒的全基因组序列,估算该病毒8个基因结构区及整体的进化率,为进一步探索H7N9的进化机制提供理论支持。方法选取全球共享禽流感数据倡议组织(GISAID)中以人类为宿主的H7N9病毒基因序列,同时合并与新型H7N9的6个内部基因结构区具有高度同源性的H9N2序列;采用Bio Edit7.0软件进行多序列比对,MEGA 6.06建立系统发育树;利用Path-o-gen软件初步估算进化率,并以此作为先验信息,基于分子时钟和蒙特卡罗马尔科夫链(MCMC)模型进一步估算H7N9各基因结构区的进化率。结果进化率结果表明H7N9禽流感病毒进化快,全基因进化率为4.60×10~(–3)次/位点/年(95%CI=3.94×10~(–3)~5.40×10~(–3)),血凝素(HA)和神经氨酸酶(NA)具有较快的进化率,分别为7.43×10~(–3)和5.92×10~(–3)次/位点/年,聚合酶A(PA)、聚合酶B1(PB1)和聚合酶B2(PB2)进化速度也相对较其他基因片段快。结论 H7N9病毒进化速度快,急需建立一个有效长期的流感病毒监测制度。
Objective To assess the evolutionary rate of novel influenza A H7N9 virus based on the full length sequences and to provide a theoretical guidance for making prevention and control strategies.Methods The sequences of the influenza A H7N9 virus from The Global Initiative on Sharing Avian Influenza Data(GISAID) were used to construct phylogenetic trees using programs Bio Edit 7.0 and MEGA 6.06.Preliminary evolutionary rates were estimated with Path-o-gen; then using the preliminary rates as prior information,we further estimated the rates with BEAST 1.8.2 based on molecular clock and Monte Carlo Markov Chain(MCMC) model.Results High evolutionary rates of the novel influenza A H7N9 virus were observed.The mean evolutionary rate for full-length genomic sequences is 4.60 × 10~(–3)(95% highest probability density[HPD]:3.94 × 10~(–3),5.40 × 10~(–3)) subs/site/year.The evolutionary rate of nucleotide substitution of haemagglutinin and neuraminidase(7.43 and 5.92 × 10~(–3) subs/site/year) are higher than the evolutionary rate of the H7N9 and higher evolutionary rates of polymerase A(PA),polymerase B1(PB1),and polymerase B2(PB2) genes were also observed.Conclusion The novel influenza A H7N9 virus evolves at a high rate,suggesting that effective and long-term surveillance should be carried out.
Objective To assess the evolutionary rate of novel influenza A H7N9 virus based on the full length sequences and to provide a theoretical guidance for making prevention and control strategies.Methods The sequences of the influenza A H7N9 virus from The Global Initiative on Sharing Avian Influenza Data(GISAID) were used to construct phylogenetic trees using programs Bio Edit 7.0 and MEGA 6.06.Preliminary evolutionary rates were estimated with Path-o-gen; then using the preliminary rates as prior information,we further estimated the rates with BEAST 1.8.2 based on molecular clock and Monte Carlo Markov Chain(MCMC) model.Results High evolutionary rates of the novel influenza A H7N9 virus were observed.The mean evolutionary rate for full-length genomic sequences is 4.60 × 10~(–3)(95% highest probability density[HPD]:3.94 × 10~(–3),5.40 × 10~(–3)) subs/site/year.The evolutionary rate of nucleotide substitution of haemagglutinin and neuraminidase(7.43 and 5.92 × 10~(–3) subs/site/year) are higher than the evolutionary rate of the H7N9 and higher evolutionary rates of polymerase A(PA),polymerase B1(PB1),and polymerase B2(PB2) genes were also observed.Conclusion The novel influenza A H7N9 virus evolves at a high rate,suggesting that effective and long-term surveillance should be carried out.
引文
[1]Drummond A,Pybus OG,Rambaut A.Inference of viral evolutionary rates from molecular sequences[J].Advances in Parasitology,2003,54(54):331-358.
[2]Husain M.Avian influenza A(H7N9)virus infection in humans:epidemiology,evolution,and pathogenesis[J].Infection Genetics and Evolution:Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases,2014,28:304-312.
[3]Fridley BL.Bayesian variable and model selection methods for genetic association studies[J].Genetic Epidemiology,2009,33(1):27-37.
[4]Ho SYW,Duchêne S.Molecular-clock methods for estimating evolutionary rates and timescales[J].Molecular Ecology,2014,23(24):5947-5965.
[5]Berry IM,Ribeiro R,Kothari M,et al.Unequal evolutionary rates in the human immunodeficiency virus type 1(HIV-1)pandemic:the evolutionary rate of HIV-1 slows down when the epidemic rate increases[J].Journal of Virology,2007,81(19):10625-10635.
[6]Yuan M,Lu T,Li C,et al.The evolutionary rates of HCVestimated with subtype 1a and 1b sequences over the ORF length and in different genomic regions[J].PLo S One,2013,8(6):e64698.
[7]Lam TT,Wang J,Shen Y,et al.The genesis and source of the H7N9 influenza viruses causing human infections in China[J].Nature,2013,502(7470):241-244.
[8]Liu W,Fan H,Raghwani J,et al.Occurrence and reassortment of avian influenza A(H7N9)viruses derived from coinfected birds in China[J].Virology,2014,88:13344-13351.
[9]He J,Ning L,Tong Y.Origins and evolutionary genomics of the novel 2013 avian-origin H7N9 influenza A virus in China:early findings[J/OL].[2013-04-09].http://arxiv.org/abs/1304.1985.
[10]Lam TT,Zhou B,Wang J,et al.Dissemination,divergence and establishment of H7N9 influenza viruses in China[J].Nature,2015,522:102-105.
[11]Zhu W,Shu Y.Genetic tuning of avian influenza A(H7N9)virus promotes viral fitness within different species[J].Microbes and Infection/Institut Pasteur,2015,17(2):118-122.
[12]Liu M,Song T,Hua S,et al.Computational analysis of antigenic epitopes of avian influenza A(H7N9)viruses[J].Science China Life Sciences,2015,58(7):687-693.
[13]Rejmanek D,Hosseini PR,Mazet JA,et al.Evolutionary dynamics and global diversity of influenza A virus[J].Journal of Virology,2015,89(21):10993-11001.
[14]万勇汤.甲型N9亚型流感病毒神经氨酸酶基因进化分析[J].病毒学报,2015,31(2):139-144.
[15]Gao R,Cao B,Hu Y,et al.Human infection with a novel avianorigin influenza A(H7N9)virus[J].The New England Journal of Medicine,2013,368(20):1888-1897.
[16]Schrauwen EJ,Richard M,Burke DF,et al.Amino acid substitutions that affect receptor binding and stability of the hemagglutinin of influenza A/H7N9 virus[J].Journal of Virology,2016,90(7):3794-3799.
[17]Gillman A,Nykvist M,Muradrasoli S,et al.Influenza A(H7N9)virus acquires resistance-related neuraminidase I222T substitution when infected mallards are exposed to low levels of oseltamivir in water[J].Antimicrobial Agents and Chemotherapy,2015,59(9):5196-5202.
[18]Chen L,Sun L,Li R,et al.Is a highly pathogenic avian influenza virus H5N1 fragment recombined in PB1 the key for the epidemic of the novel AIV H7N9 in China,2013?[J].International Journal of Infectious Diseases,2016,43:85-89.
[19]Su W,Wang C,Luo J,et al.Testing the effect of internal genes derived from a wild-bird-origin H9N2 influenza A virus on the pathogenicity of an A/H7N9 virus[J].Cell Reports,2015,12(11):1831-1841.
[2]Husain M.Avian influenza A(H7N9)virus infection in humans:epidemiology,evolution,and pathogenesis[J].Infection Genetics and Evolution:Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases,2014,28:304-312.
[3]Fridley BL.Bayesian variable and model selection methods for genetic association studies[J].Genetic Epidemiology,2009,33(1):27-37.
[4]Ho SYW,Duchêne S.Molecular-clock methods for estimating evolutionary rates and timescales[J].Molecular Ecology,2014,23(24):5947-5965.
[5]Berry IM,Ribeiro R,Kothari M,et al.Unequal evolutionary rates in the human immunodeficiency virus type 1(HIV-1)pandemic:the evolutionary rate of HIV-1 slows down when the epidemic rate increases[J].Journal of Virology,2007,81(19):10625-10635.
[6]Yuan M,Lu T,Li C,et al.The evolutionary rates of HCVestimated with subtype 1a and 1b sequences over the ORF length and in different genomic regions[J].PLo S One,2013,8(6):e64698.
[7]Lam TT,Wang J,Shen Y,et al.The genesis and source of the H7N9 influenza viruses causing human infections in China[J].Nature,2013,502(7470):241-244.
[8]Liu W,Fan H,Raghwani J,et al.Occurrence and reassortment of avian influenza A(H7N9)viruses derived from coinfected birds in China[J].Virology,2014,88:13344-13351.
[9]He J,Ning L,Tong Y.Origins and evolutionary genomics of the novel 2013 avian-origin H7N9 influenza A virus in China:early findings[J/OL].[2013-04-09].http://arxiv.org/abs/1304.1985.
[10]Lam TT,Zhou B,Wang J,et al.Dissemination,divergence and establishment of H7N9 influenza viruses in China[J].Nature,2015,522:102-105.
[11]Zhu W,Shu Y.Genetic tuning of avian influenza A(H7N9)virus promotes viral fitness within different species[J].Microbes and Infection/Institut Pasteur,2015,17(2):118-122.
[12]Liu M,Song T,Hua S,et al.Computational analysis of antigenic epitopes of avian influenza A(H7N9)viruses[J].Science China Life Sciences,2015,58(7):687-693.
[13]Rejmanek D,Hosseini PR,Mazet JA,et al.Evolutionary dynamics and global diversity of influenza A virus[J].Journal of Virology,2015,89(21):10993-11001.
[14]万勇汤.甲型N9亚型流感病毒神经氨酸酶基因进化分析[J].病毒学报,2015,31(2):139-144.
[15]Gao R,Cao B,Hu Y,et al.Human infection with a novel avianorigin influenza A(H7N9)virus[J].The New England Journal of Medicine,2013,368(20):1888-1897.
[16]Schrauwen EJ,Richard M,Burke DF,et al.Amino acid substitutions that affect receptor binding and stability of the hemagglutinin of influenza A/H7N9 virus[J].Journal of Virology,2016,90(7):3794-3799.
[17]Gillman A,Nykvist M,Muradrasoli S,et al.Influenza A(H7N9)virus acquires resistance-related neuraminidase I222T substitution when infected mallards are exposed to low levels of oseltamivir in water[J].Antimicrobial Agents and Chemotherapy,2015,59(9):5196-5202.
[18]Chen L,Sun L,Li R,et al.Is a highly pathogenic avian influenza virus H5N1 fragment recombined in PB1 the key for the epidemic of the novel AIV H7N9 in China,2013?[J].International Journal of Infectious Diseases,2016,43:85-89.
[19]Su W,Wang C,Luo J,et al.Testing the effect of internal genes derived from a wild-bird-origin H9N2 influenza A virus on the pathogenicity of an A/H7N9 virus[J].Cell Reports,2015,12(11):1831-1841.