Genome Analysis of Coxsackievirus A4 Isolates From Hand, Foot, and Mouth Disease Cases in Shandong, China
Coxsackievirus A4 (CVA4) is one of the most prevalent pathogens associated with hand, foot and mouth disease (HFMD), an acute febrile illness in children, and is also associated with acute localized exanthema, myocarditis, hepatitis and pancreatitis. Despite this, limited CVA4 genome sequences are c...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-05-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2019.01001/full |
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| author | Min Wang Juan Li Ming-Xiao Yao Ya-Wei Zhang Tao Hu Michael J. Carr Michael J. Carr Sebastián Duchêne Xing-Cheng Zhang Zhen-Jie Zhang Hong Zhou Yi-Gang Tong Shu-Jun Ding Xian-Jun Wang Wei-Feng Shi |
| author_facet | Min Wang Juan Li Ming-Xiao Yao Ya-Wei Zhang Tao Hu Michael J. Carr Michael J. Carr Sebastián Duchêne Xing-Cheng Zhang Zhen-Jie Zhang Hong Zhou Yi-Gang Tong Shu-Jun Ding Xian-Jun Wang Wei-Feng Shi |
| author_sort | Min Wang |
| collection | DOAJ |
| description | Coxsackievirus A4 (CVA4) is one of the most prevalent pathogens associated with hand, foot and mouth disease (HFMD), an acute febrile illness in children, and is also associated with acute localized exanthema, myocarditis, hepatitis and pancreatitis. Despite this, limited CVA4 genome sequences are currently available. Herein, complete genome sequences from CVA4 strains (n = 21), isolated from patients with HFMD in Shandong province, China between 2014 and 2016, were determined and phylogenetically characterized. Phylogenetic analysis of the VP1 gene from a larger CVA4 collection (n = 175) showed that CVA4 has evolved into four separable genotypes: A, B, C, and D; and genotype D could be further classified in to two sub-genotypes: D1 and D2. Each of the 21 newly described genomes derived from isolates that segregated with sub-genotype D2. The CVA4 genomes displayed significant intra-genotypic genetic diversity with frequent synonymous substitutions occurring at the third codon positions, particularly within the P2 region. However, VP1 was relatively stable and therefore represents a potential target for molecular diagnostics assays and also for the rational design of vaccine epitopes. The substitution rate of VP1 was estimated to be 5.12 × 10-3 substitutions/site/year, indicative of ongoing CVA4 evolution. Mutations at amino acid residue 169 in VP1 gene may be responsible for differing virulence of CVA4 strains. Bayesian skyline plot analysis showed that the population size of CVA4 has experienced several dynamic fluctuations since 1948. In summary, we describe the phylogenetic and molecular characterization of 21 complete genomes from CVA4 isolates which greatly enriches the known genomic diversity of CVA4 and underscores the need for further surveillance of CVA4 in China. |
| first_indexed | 2024-12-21T19:10:11Z |
| format | Article |
| id | doaj.art-4e91462e968a419a9aca9f4a0b90a064 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-21T19:10:11Z |
| publishDate | 2019-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Microbiology |
| spelling | doaj.art-4e91462e968a419a9aca9f4a0b90a0642022-12-21T18:53:14ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-05-011010.3389/fmicb.2019.01001451746Genome Analysis of Coxsackievirus A4 Isolates From Hand, Foot, and Mouth Disease Cases in Shandong, ChinaMin Wang0Juan Li1Ming-Xiao Yao2Ya-Wei Zhang3Tao Hu4Michael J. Carr5Michael J. Carr6Sebastián Duchêne7Xing-Cheng Zhang8Zhen-Jie Zhang9Hong Zhou10Yi-Gang Tong11Shu-Jun Ding12Xian-Jun Wang13Wei-Feng Shi14Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Taishan Medical College, Tai’an, ChinaKey Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Taishan Medical College, Tai’an, ChinaShandong Provincial Key Laboratory of Communicable Disease Control and Prevention, Institute for Viral Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, ChinaKey Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Taishan Medical College, Tai’an, ChinaGlobal Station for Zoonosis Control, Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo, JapanNational Virus Reference Laboratory, School of Medicine, University College Dublin, Dublin, IrelandDepartment of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, AustraliaKey Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Taishan Medical College, Tai’an, ChinaKey Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Taishan Medical College, Tai’an, ChinaKey Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Taishan Medical College, Tai’an, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, ChinaShandong Provincial Key Laboratory of Communicable Disease Control and Prevention, Institute for Viral Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, ChinaShandong Provincial Key Laboratory of Communicable Disease Control and Prevention, Institute for Viral Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, ChinaKey Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Taishan Medical College, Tai’an, ChinaCoxsackievirus A4 (CVA4) is one of the most prevalent pathogens associated with hand, foot and mouth disease (HFMD), an acute febrile illness in children, and is also associated with acute localized exanthema, myocarditis, hepatitis and pancreatitis. Despite this, limited CVA4 genome sequences are currently available. Herein, complete genome sequences from CVA4 strains (n = 21), isolated from patients with HFMD in Shandong province, China between 2014 and 2016, were determined and phylogenetically characterized. Phylogenetic analysis of the VP1 gene from a larger CVA4 collection (n = 175) showed that CVA4 has evolved into four separable genotypes: A, B, C, and D; and genotype D could be further classified in to two sub-genotypes: D1 and D2. Each of the 21 newly described genomes derived from isolates that segregated with sub-genotype D2. The CVA4 genomes displayed significant intra-genotypic genetic diversity with frequent synonymous substitutions occurring at the third codon positions, particularly within the P2 region. However, VP1 was relatively stable and therefore represents a potential target for molecular diagnostics assays and also for the rational design of vaccine epitopes. The substitution rate of VP1 was estimated to be 5.12 × 10-3 substitutions/site/year, indicative of ongoing CVA4 evolution. Mutations at amino acid residue 169 in VP1 gene may be responsible for differing virulence of CVA4 strains. Bayesian skyline plot analysis showed that the population size of CVA4 has experienced several dynamic fluctuations since 1948. In summary, we describe the phylogenetic and molecular characterization of 21 complete genomes from CVA4 isolates which greatly enriches the known genomic diversity of CVA4 and underscores the need for further surveillance of CVA4 in China.https://www.frontiersin.org/article/10.3389/fmicb.2019.01001/fullCoxsackievirus A4handfootand mouth diseasegenotypesphylogenetic analysis |
| spellingShingle | Min Wang Juan Li Ming-Xiao Yao Ya-Wei Zhang Tao Hu Michael J. Carr Michael J. Carr Sebastián Duchêne Xing-Cheng Zhang Zhen-Jie Zhang Hong Zhou Yi-Gang Tong Shu-Jun Ding Xian-Jun Wang Wei-Feng Shi Genome Analysis of Coxsackievirus A4 Isolates From Hand, Foot, and Mouth Disease Cases in Shandong, China Frontiers in Microbiology Coxsackievirus A4 hand foot and mouth disease genotypes phylogenetic analysis |
| title | Genome Analysis of Coxsackievirus A4 Isolates From Hand, Foot, and Mouth Disease Cases in Shandong, China |
| title_full | Genome Analysis of Coxsackievirus A4 Isolates From Hand, Foot, and Mouth Disease Cases in Shandong, China |
| title_fullStr | Genome Analysis of Coxsackievirus A4 Isolates From Hand, Foot, and Mouth Disease Cases in Shandong, China |
| title_full_unstemmed | Genome Analysis of Coxsackievirus A4 Isolates From Hand, Foot, and Mouth Disease Cases in Shandong, China |
| title_short | Genome Analysis of Coxsackievirus A4 Isolates From Hand, Foot, and Mouth Disease Cases in Shandong, China |
| title_sort | genome analysis of coxsackievirus a4 isolates from hand foot and mouth disease cases in shandong china |
| topic | Coxsackievirus A4 hand foot and mouth disease genotypes phylogenetic analysis |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2019.01001/full |
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