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目的 分析山东3株埃可病毒18型（echovirus 18，E18）分离株的遗传特征，探明E18病毒的进化规律。 方法 采集2019—2020年山东省手足口病患者和疱疹性咽峡炎患者的血清样本，通过病毒分离、荧光定量检测和高通量测序，共获得3株E18分离株及其全基因组序列；利用MEGA 11和Bioedit软件进行E18病毒株VP1基因和全基因组序列的系统发育分析，采用Simplot软件和RDP软件进行重组分析，研究E18病毒株的遗传特征。 结果 3株E18分离株基因组序列长度分别为7 367、7 347和7 383 bp，分离株间呈较高核苷酸相似性（97.92% ~ 98.31%）和氨基酸相似性（99.11% ~ 99.28%）；3株E18分离株VP1基因位于我国主要流行基因型C基因亚型C2分支中，与我国流行的多数毒株均位于全基因组系统发育树的Group D分支。重组分析表明，3株E18分离株均为基因重组株，毒株基因组P2和P3区约4 620 ~ 7 200位点间与国内E30流行株A86/YN相似性较高。 结论 E18毒株在我国多地持续流行，3株山东分离株同国内多数E18株的VP1基因和全基因组均位于同一进化分支，它们所在C2基因型为国内VP1基因流行亚型，全基因组Group D为国内优势流行分支。E18毒株在P2和P3区与E30发生潜在型间重组，对E18的遗传多样性研究具有参考意义。
","endNoteUrl_en":"http://xuebao.sdfmu.edu.cn/EN/article/getTxtFile.do?fileType=EndNote&id=747","reference":"| 1 | International Committee on Taxonomy of Viruses （ICTV）. Master species lists （MSL）［EB/OL］. ［2024/5/28］. . |
| 2 | Andersson P， Edman K， Lindberg AM. Molecular analysis of the echovirus 18 prototype： evidence of interserotypic recombination with echovirus 9［J］. Virus Res， 2002， 85（1）： 71. |
| 3 | Wilfert CM， Lauer BA， Cohen M， et al. An epidemic of echovirus 18 meningitis［J］. J Infect Dis， 1975， 131（1）： 75. |
| 4 | Miyamura K， Yamashita K， Yamadera S， et al. An epidemic of echovirus 18 in 1988 in Japan--high association with clinical manifestation of exanthem. A report of the national epidemiological surveillance of infectious agents in Japan［J］. Jpn J Med Sci Biol， 1990， 43（2）： 51. |
| 5 | Baek K， Park K， Jung E， et al. Molecular and epidemiological characterization of enteroviruses isolated in Chungnam， Korea from 2005 to 2006［J］. J Microbiol Biotechnol， 2009， 19（9）： 1055. |
| 6 | Krumbholz A， Egerer R， Braun H， et al. Analysis of an echovirus 18 outbreak in Thuringia， Germany： insights into the molecular epidemiology and evolution of several enterovirus species B members［J］. Med Microbiol Immunol， 2016， 205（5）： 471. |
| 7 | Brunel D， Jacques J， Motte J， et al. Fatal echovirus 18 leukoencephalitis in a child［J］. J Clin Microbiol， 2007， 45（6）： 2068. |
| 8 | Chen XP， Ji TJ， Guo JY， et al. Molecular epidemiology of echovirus 18 circulating in mainland China from 2015 to 2016［J］. Virol Sin， 2019， 34（1）： 50. |
| 9 | 张名， 许丹菡， 冯昌增， 等. 2019年云南省埃可病毒18型分离株的全基因组分析［J］. 中国病原生物学杂志， 2021， 16（8）： 888. |
| 10 | 周健明， 谢显清， 方苓， 等. 引起一起暴发性急性胃肠炎疫情的埃可病毒18型VP1基因特征分析［J］. 病毒学报， 2021， 37（1）： 133. |
| 11 | Tsai HP， Huang SW， Wu FL， et al. An echovirus 18-associated outbreak of aseptic meningitis in Taiwan： epidemiology and diagnostic and genetic aspects［J］. J Med Microbiol， 2011， 60（Pt 9）： 1360. |
| 12 | 卫生部. 手足口病预防控制指南（2009版）［J］. 全科医学临床与教育， 2010， 8（2）： 125. |
| 13 | Zhang ZJ， Dong ZP， Li J， et al. Protective efficacies of formaldehyde-inactivated whole-virus vaccine and antivirals in a murine model of coxsackievirus A10 infection［J］. J Virol， 2017， 91（13）： e00333. |
| 14 | Tamura K， Stecher G， Kumar S. MEGA11： molecular evolutionary genetics analysis version 11［J］. Mol Biol Evol， 2021， 38（7）： 3022. |
| 15 | Stamatakis A， Ludwig T， Meier H. RAxML-III： a fast program for maximum likelihood-based inference of large phylogenetic trees［J］. Bioinformatics， 2005， 21（4）： 456. |
| 16 | Lole KS， Bollinger RC， Paranjape RS， et al. Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India， with evidence of intersubtype recombination［J］. J Virol，1999，73（1）：152. |
| 17 | Martin D， Rybicki E. RDP： detection of recombination amongst aligned sequences［J］. Bioinformatics， 2000， 16（6）： 562. |
| 18 | Khetsuriani N， Lamonte-Fowlkes A， Oberst S， et al. Enterovirus surveillance--United States， 1970-2005［J］. MMWR Surveill Summ， 2006， 55（8）： 1. |
| 19 | Abedi GR， Watson JT， Pham H， et al. Enterovirus and human parechovirus surveillance - United States， 2009-2013［J］. MMWR Morb Mortal Wkly Rep， 2015， 64（34）： 940. |
| 20 | Zhang HH， Zhao YL， Liu HB， et al. Molecular characterization of two novel echovirus 18 recombinants associated with hand-foot-mouth disease［J］. Sci Rep， 2017， 7（1）： 8448. |
| 21 | 南巍巍. 2019年—2020年住院手足口病患儿临床特点及肠道病毒分子流行病学研究［D］. 大理： 大理大学， 2021. |
| 22 | Oberste MS， Maher K， Kilpatrick DR， et al. Typing of human enteroviruses by partial sequencing of VP1［J］. J Clin Microbiol， 1999， 37（5）： 1288. |
| 23 | Wang M， Li J， Yao MX， et al. Genome analysis of coxsackievirus a4 isolates from hand， foot， and mouth disease cases in Shandong， China［J］. Front Microbiol， 2019， 10： 1001. |
| 24 | 王敏， 韦庆娟， 李娟， 等. 2013～2014年山东省4株柯萨奇B4型分离株遗传分析［J］. 病毒学报， 2018， 34（1）： 22. |
| 25 | Hu YF， Yang F， Du J， et al. Complete genome analysis of coxsackievirus A2， A4， A5， and A10 strains isolated from hand， foot， and mouth disease patients in China revealing frequent recombination of human enterovirus A［J］. J Clin Microbiol， 2011， 49（7）： 2426. |
| 26 | Rico-Hesse R， Pallansch MA， Nottay BK， et al. Geographic distribution of wild poliovirus type 1 genotypes［J］. Virology （Lond）， 1987， 160（2）： 311. |
| 27 | Jiang CM， Xu ZX， Li J， et al. Case report： clinical and virological characteristics of aseptic meningitis caused by a recombinant echovirus 18 in an immunocompetent adult［J］. Front Med （Lausanne）， 2023， 9： 1094347. |
)","risUrl_cn":"//www.pitakata.com/xuebao/CN/article/getTxtFile.do?fileType=Ris&id=747","title_cn":"埃可病毒18型山东分离株遗传特征分析","doi":"10.3969/j.issn.2097-0005.2025.01.002","jieShuYe":"16","keywordList_en":["enterovirus","echovirus 18","genetic characteristic analysis","recombination analysis"],"endNoteUrl_cn":"//www.pitakata.com/xuebao/CN/article/getTxtFile.do?fileType=EndNote&id=747","zhaiyao_en":"Objective To investigate the genetic characteristics of three echovirus 18 （E18） strains isolated from Shandong Province， and to explore the evolutionary patterns of E18 strains. Methods Serum samples were collected from patients with hand， foot and mouth disease and patients with herpangina in Shandong Province from 2019 to 2020. Through virus isolation， RT-qPCR amplification， and high-throughput sequencing， three E18 isolates were identified， and their whole-genome sequences were obtained. Phylogenetic trees were constructed based on the the full-length VP1 gene sequences and the complete genome sequences and of E18 strains using MEGA 11 and Bioedit. Recombination analysis was performed using Simplot and RDP. Results Full-length genomes of the three E18 isolates were 7 367 bp， 7 347 bp and 7 383 bp in length， respectively. They showed high nucleotide （97.92% – 98.31%） and amino acid （99.11% – 99.28%） similarities. Phylogenetic analysis showed that the VP1 gene sequences of the three E18 strains were classified into the subgenotype C2，and their complete genome sequences clustered together with the majority of the Chinese strains within Group D， and their. Recombination analysis indicated that the three E18 isolates were potential recombinants with the P2 and P3 regions likely recombined from the Chinese E30 strain A86/YN （4 620 bp – 7 200 bp）. Conclusion Our results highlight the constant circulation of E18 in China. The three E18 strains from Shandong Province were grouped together with the dominant E18 strains circulating in China. This suggests that they belong to the prevalent lineages： subgenotype C2 of the VP1 gene and the Group D of the complete genome. It also indicated that the potential inter-typic recombination had occurred between E18 and E30 in the P2 and P3 regions， providing insights into the genetic diversity of E18.
","bibtexUrl_en":"http://xuebao.sdfmu.edu.cn/EN/article/getTxtFile.do?fileType=BibTeX&id=747","abstractUrl_cn":"http://xuebao.sdfmu.edu.cn/CN/10.3969/j.issn.2097-0005.2025.01.002","zuoZheCn_L":"刘棋, 徐险峰, 王敏, 邢薇佳, 史卫峰, 李娟","juanUrl_cn":"http://xuebao.sdfmu.edu.cn/CN/Y2025","lanMu_en":"Research in Enterovirus","qiUrl_en":"http://xuebao.sdfmu.edu.cn/EN/Y2025/V46/I1","zuoZhe_EN":"Qi LIU1,2, Xianfeng XU1,3, Min WANG4, Weijia XING1,5, Weifeng SHI6,7, Juan LI1,2,5()","risUrl_en":"http://xuebao.sdfmu.edu.cn/EN/article/getTxtFile.do?fileType=Ris&id=747","title_en":"Genetic characterizations of echovirus 18 strains isolated from Shandong province， China","hasPdf":"true"},"authorNotes_cn":["李娟，E-mail： lijuan@sdfmu.edu.cn。
埃可病毒18型山东分离株遗传特征分析
刘棋, 徐险峰, 王敏, 邢薇佳, 史卫峰, 李娟
betway必威登陆网址 (betway.com )学报››2025, Vol. 46››Issue (1): 9-16.
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埃可病毒18型山东分离株遗传特征分析
Genetic characterizations of echovirus 18 strains isolated from Shandong province， China
目的分析山东3株埃可病毒18型（echovirus 18，E18）分离株的遗传特征，探明E18病毒的进化规律。方法采集2019—2020年山东省手足口病患者和疱疹性咽峡炎患者的血清样本，通过病毒分离、荧光定量检测和高通量测序，共获得3株E18分离株及其全基因组序列；利用MEGA 11和Bioedit软件进行E18病毒株VP1基因和全基因组序列的系统发育分析，采用Simplot软件和RDP软件进行重组分析，研究E18病毒株的遗传特征。结果3株E18分离株基因组序列长度分别为7 367、7 347和7 383 bp，分离株间呈较高核苷酸相似性（97.92% ~ 98.31%）和氨基酸相似性（99.11% ~ 99.28%）；3株E18分离株VP1基因位于我国主要流行基因型C基因亚型C2分支中，与我国流行的多数毒株均位于全基因组系统发育树的Group D分支。重组分析表明，3株E18分离株均为基因重组株，毒株基因组P2和P3区约4 620 ~ 7 200位点间与国内E30流行株A86/YN相似性较高。结论E18毒株在我国多地持续流行，3株山东分离株同国内多数E18株的VP1基因和全基因组均位于同一进化分支，它们所在C2基因型为国内VP1基因流行亚型，全基因组Group D为国内优势流行分支。E18毒株在P2和P3区与E30发生潜在型间重组，对E18的遗传多样性研究具有参考意义。
ObjectiveTo investigate the genetic characteristics of three echovirus 18 （E18） strains isolated from Shandong Province， and to explore the evolutionary patterns of E18 strains.MethodsSerum samples were collected from patients with hand， foot and mouth disease and patients with herpangina in Shandong Province from 2019 to 2020. Through virus isolation， RT-qPCR amplification， and high-throughput sequencing， three E18 isolates were identified， and their whole-genome sequences were obtained. Phylogenetic trees were constructed based on the the full-length VP1 gene sequences and the complete genome sequences and of E18 strains using MEGA 11 and Bioedit. Recombination analysis was performed using Simplot and RDP.ResultsFull-length genomes of the three E18 isolates were 7 367 bp， 7 347 bp and 7 383 bp in length， respectively. They showed high nucleotide （97.92% – 98.31%） and amino acid （99.11% – 99.28%） similarities. Phylogenetic analysis showed that the VP1 gene sequences of the three E18 strains were classified into the subgenotype C2，and their complete genome sequences clustered together with the majority of the Chinese strains within Group D， and their. Recombination analysis indicated that the three E18 isolates were potential recombinants with the P2 and P3 regions likely recombined from the Chinese E30 strain A86/YN （4 620 bp – 7 200 bp）.ConclusionOur results highlight the constant circulation of E18 in China. The three E18 strains from Shandong Province were grouped together with the dominant E18 strains circulating in China. This suggests that they belong to the prevalent lineages： subgenotype C2 of the VP1 gene and the Group D of the complete genome. It also indicated that the potential inter-typic recombination had occurred between E18 and E30 in the P2 and P3 regions， providing insights into the genetic diversity of E18.
enterovirus/echovirus 18/genetic characteristic analysis/recombination analysis
| 1 | International Committee on Taxonomy of Viruses （ICTV）. Master species lists （MSL）［EB/OL］. ［2024/5/28］. . |
| 2 | Andersson P， Edman K， Lindberg AM. Molecular analysis of the echovirus 18 prototype： evidence of interserotypic recombination with echovirus 9［J］.Virus Res，2002，85（1）： 71. |
| 3 | Wilfert CM， Lauer BA， Cohen M， et al. An epidemic of echovirus 18 meningitis［J］.J Infect Dis，1975，131（1）： 75. |
| 4 | Miyamura K， Yamashita K， Yamadera S， et al. An epidemic of echovirus 18 in 1988 in Japan--high association with clinical manifestation of exanthem. A report of the national epidemiological surveillance of infectious agents in Japan［J］.Jpn J Med Sci Biol，1990，43（2）： 51. |
| 5 | Baek K， Park K， Jung E， et al. Molecular and epidemiological characterization of enteroviruses isolated in Chungnam， Korea from 2005 to 2006［J］.J Microbiol Biotechnol，2009，19（9）： 1055. |
| 6 | Krumbholz A， Egerer R， Braun H， et al. Analysis of an echovirus 18 outbreak in Thuringia， Germany： insights into the molecular epidemiology and evolution of several enterovirus species B members［J］.Med Microbiol Immunol，2016，205（5）： 471. |
| 7 | Brunel D， Jacques J， Motte J， et al. Fatal echovirus 18 leukoencephalitis in a child［J］.J Clin Microbiol，2007，45（6）： 2068. |
| 8 | Chen XP， Ji TJ， Guo JY， et al. Molecular epidemiology of echovirus 18 circulating in mainland China from 2015 to 2016［J］.Virol Sin，2019，34（1）： 50. |
| 9 | 张名， 许丹菡， 冯昌增， 等. 2019年云南省埃可病毒18型分离株的全基因组分析［J］.中国病原生物学杂志，2021，16（8）： 888. |
| 10 | 周健明， 谢显清， 方苓， 等. 引起一起暴发性急性胃肠炎疫情的埃可病毒18型VP1基因特征分析［J］.病毒学报，2021，37（1）： 133. |
| 11 | Tsai HP， Huang SW， Wu FL， et al. An echovirus 18-associated outbreak of aseptic meningitis in Taiwan： epidemiology and diagnostic and genetic aspects［J］.J Med Microbiol，2011，60（Pt 9）： 1360. |
| 12 | 卫生部. 手足口病预防控制指南（2009版）［J］.全科医学临床与教育，2010，8（2）： 125. |
| 13 | Zhang ZJ， Dong ZP， Li J， et al. Protective efficacies of formaldehyde-inactivated whole-virus vaccine and antivirals in a murine model of coxsackievirus A10 infection［J］.J Virol，2017，91（13）： e00333. |
| 14 | Tamura K， Stecher G， Kumar S. MEGA11： molecular evolutionary genetics analysis version 11［J］.Mol Biol Evol，2021，38（7）： 3022. |
| 15 | Stamatakis A， Ludwig T， Meier H. RAxML-III： a fast program for maximum likelihood-based inference of large phylogenetic trees［J］.Bioinformatics，2005，21（4）： 456. |
| 16 | Lole KS， Bollinger RC， Paranjape RS， et al. Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India， with evidence of intersubtype recombination［J］.J Virol，1999，73（1）：152. |
| 17 | Martin D， Rybicki E. RDP： detection of recombination amongst aligned sequences［J］.Bioinformatics，2000，16（6）： 562. |
| 18 | Khetsuriani N， Lamonte-Fowlkes A， Oberst S， et al. Enterovirus surveillance--United States， 1970-2005［J］.MMWR Surveill Summ，2006，55（8）： 1. |
| 19 | Abedi GR， Watson JT， Pham H， et al. Enterovirus and human parechovirus surveillance - United States， 2009-2013［J］.MMWR Morb Mortal Wkly Rep，2015，64（34）： 940. |
| 20 | Zhang HH， Zhao YL， Liu HB， et al. Molecular characterization of two novel echovirus 18 recombinants associated with hand-foot-mouth disease［J］.Sci Rep，2017，7（1）： 8448. |
| 21 | 南巍巍. 2019年—2020年住院手足口病患儿临床特点及肠道病毒分子流行病学研究［D］. 大理： 大理大学，2021. |
| 22 | Oberste MS， Maher K， Kilpatrick DR， et al. Typing of human enteroviruses by partial sequencing of VP1［J］.J Clin Microbiol，1999，37（5）： 1288. |
| 23 | Wang M， Li J， Yao MX， et al. Genome analysis of coxsackievirus a4 isolates from hand， foot， and mouth disease cases in Shandong， China［J］.Front Microbiol，2019，10： 1001. |
| 24 | 王敏， 韦庆娟， 李娟， 等. 2013～2014年山东省4株柯萨奇B4型分离株遗传分析［J］.病毒学报，2018，34（1）： 22. |
| 25 | Hu YF， Yang F， Du J， et al. Complete genome analysis of coxsackievirus A2， A4， A5， and A10 strains isolated from hand， foot， and mouth disease patients in China revealing frequent recombination of human enterovirus A［J］.J Clin Microbiol，2011，49（7）： 2426. |
| 26 | Rico-Hesse R， Pallansch MA， Nottay BK， et al. Geographic distribution of wild poliovirus type 1 genotypes［J］.Virology （Lond），1987，160（2）： 311. |
| 27 | Jiang CM， Xu ZX， Li J， et al. Case report： clinical and virological characteristics of aseptic meningitis caused by a recombinant echovirus 18 in an immunocompetent adult［J］.Front Med （Lausanne），2023，9： 1094347. |
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