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作者

Wang, M. Li, J. Yao, M.-X. Zhang, Y.-W. Hu, T. Carr, M.J. Duchêne, S. Zhang, X.-C. Zhang, Z.-J. Zhou, H. Tong, Y.-G. Ding, S.-J. Wang, X.-J. Shi, W.-F.

作者单位

National Virus Reference Laboratory, School of Medicine, University College Dublin, Dublin, Ireland State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China Shandong Provincial Key Laboratory of Communicable Disease Control and Prevention, Institute for Viral Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, China Shandong Provincial Key Laboratory of Communicable Disease Control and Prevention, Institute for Viral Dis Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, China f Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, Australia a Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Taishan Medical College, Tai'an, China

刊名

Frontiers in Microbiology

年份

2019

卷号

Vol.10

ISSN

1664-302X

关键词

And mouth disease Coxsackievirus A4 Foot Genotypes Hand Phylogenetic analysis VP1

摘要

Coxsackievirus A4 is one of the most prevalent pathogens associated with hand, foot and mouth disease , 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 , isolated from patients with HFMD in Shandong province, China between 2014 and 2016, were determined and phylogenetically characterized. Ph...更多

Coxsackievirus A4 is one of the most prevalent pathogens associated with hand, foot and mouth disease , 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 , 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 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.收起

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