Genetic Diversity Analysis of Coxsackievirus A8 Circulating in China and Worldwide Reveals a Highly Divergent Genotype

Yang Song; Dongyan Wang; Yong Zhang; Zhenzhi Han; Jinbo Xiao; Huanhuan Lu; Dongmei Yan; Tianjiao Ji; Qian Yang; Shuangli Zhu; Wenbo Xu

doi:10.3390/v12101061

Genetic Diversity Analysis of Coxsackievirus A8 Circulating in China and Worldwide Reveals a Highly Divergent Genotype

Viruses. 2020 Sep 23;12(10):1061. doi: 10.3390/v12101061.

Authors

Yang Song¹, Dongyan Wang¹, Yong Zhang^{1

2}, Zhenzhi Han¹, Jinbo Xiao¹, Huanhuan Lu¹, Dongmei Yan¹, Tianjiao Ji¹, Qian Yang¹, Shuangli Zhu¹, Wenbo Xu^{1

2}

Affiliations

¹ WHO WPRO Regional Polio Reference Laboratory, National Health Commission Key Laboratory for Medical Virology, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, No. 155, Changbai Road, Changping District, Beijing 102206, China.
² Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China.

Abstract

Coxsackievirus A8 (CV-A8) is one of the pathogens associated with hand, foot and mouth disease (HFMD) and herpangina (HA), occasionally leading to severe neurological disorders such as acute flaccid paralysis (AFP). Only one study aimed at CV-A8 has been published to date, and only 12 whole-genome sequences are publicly available. In this study, complete genome sequences from 11 CV-A8 strains isolated from HFMD patients in extensive regions from China between 2013 and 2018 were determined, and all sequences from GenBank were retrieved. A phylogenetic analysis based on a total of 34 complete VP1 sequences of CV-A8 revealed five genotypes: A, B, C, D and E. The newly emerging genotype E presented a highly phylogenetic divergence compared with the other genotypes and was composed of the majority of the strains sequenced in this study. Markov chain Monte Carlo (MCMC) analysis revealed that genotype E has been evolving for nearly a century and somehow arose in approximately 2010. The Bayesian skyline plot showed that the population size of CV-A8 has experienced three dynamic fluctuations since 2001. Amino acid residues of VP1_100N, _103Y, _240T and _241V, which were embedded in the potential capsid loops of genotype E, might enhance genotype E adaption to the human hosts. The CV-A8 whole genomes displayed significant intra-genotypic genetic diversity in the non-capsid region, and a total of six recombinant lineages were detected. The Chinese viruses from genotype E might have emerged recently from recombining with European CV-A6 strains. CV-A8 is a less important HFMD pathogen, and the capsid gene diversity and non-capsid recombination variety observed in CV-A8 strains indicated that the constant generation of deleterious genomes and a constant selection pressure against these deleterious mutations is still ongoing within CV-A8 quasispecies. It is possible that CV-A8 could become an important pathogen in the HFMD spectrum in the future. Further surveillance of CV-A8 is greatly needed.

Keywords: and mouth disease; coxsackievirus A8; emerging diseases; evolutionary dynamics; foot; genetic diversity; hand; phylogenetic analysis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

China / epidemiology
Databases, Genetic
Enterovirus A, Human* / classification
Enterovirus A, Human* / genetics
Genetic Variation
Genome, Viral
Genotype
Hand, Foot and Mouth Disease / virology*
Humans