Molecular Epidemiology and Evolution of Coxsackievirus A9

Hehe Zhao; Jianxing Wang; Jianhua Chen; Ruifang Huang; Yong Zhang; Jinbo Xiao; Yang Song; Tianjiao Ji; Qian Yang; Shuangli Zhu; Dongyan Wang; Huanhuan Lu; Zhenzhi Han; Guoyan Zhang; Jichen Li; Dongmei Yan

doi:10.3390/v14040822

Molecular Epidemiology and Evolution of Coxsackievirus A9

Viruses. 2022 Apr 15;14(4):822. doi: 10.3390/v14040822.

Authors

Hehe Zhao¹, Jianxing Wang², Jianhua Chen³, Ruifang Huang⁴, Yong Zhang^{1

5}, Jinbo Xiao¹, Yang Song¹, Tianjiao Ji¹, Qian Yang¹, Shuangli Zhu¹, Dongyan Wang¹, Huanhuan Lu¹, Zhenzhi Han¹, Guoyan Zhang¹, Jichen Li^{1

6}, Dongmei Yan¹

Affiliations

¹ National Polio Laboratory, WHO WPRO Regional Polio Reference Laboratory, National Health Commission Key Laboratory for Biosecurity, National Health Commission Key Laboratory for Medical Virology, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
² Department for Viral Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan 250014, China.
³ Department for Viral Disease Control and Prevention, Gansu Center for Disease Control and Prevention, Lanzhou 730000, China.
⁴ Department for Communicable Disease Control and Prevention, Xinjiang Uygur Autonomous Region Center for Disease Control and Prevention, Urumqi 830011, China.
⁵ Center for Biosafety Mega-Science, Chinese Academy of Sciences, Beijing 102206, China.
⁶ Department of Medical Microbiology, Weifang Medical University, Weifang 261053, China.

Abstract

Nineteen CVA9 isolates were obtained between 2010 and 2019 from six provinces of mainland China, using the HFMD surveillance network established in China. Nucleotide sequencing revealed that the full-length VP1 of 19 CVA9 isolates was 906 bases encoding 302 amino acids. The combination of the thresholds of the phylogenetic tree and nucleotide divergence of different genotypes within the same serotype led to a value of 15-25%, and enabled CVA9 worldwide to be categorized into ten genotypes: A-J. The phylogenetic tree showed that the prototype strain was included in genotype A, and that the B, C, D, E, H, and J genotypes disappeared during virus evolution, whereas the F, I, and G genotypes showed co-circulation. Lineage G was the dominant genotype of CVA9 and included most of the strains from nine countries in Asia, North America, Oceania, and Europe. Most Chinese strains belonged to the G genotype, suggesting that the molecular epidemiology of China is consistent with that observed worldwide. The 165 partial VP1 strains (723 nt) showed a mean substitution rate of 3.27 × 10^-3 substitution/site/year (95% HPD range 2.93-3.6 × 10^-3), dating the tMRCA of CVA9 back to approximately 1922 (1911-1932). The spatiotemporal dynamics of CVA9 showed the spread of CVA9 obviously increased in recent years. Most CVA9 isolates originated in USA, but the epidemic areas of CVA9 are now concentrated in the Asia-Pacific region, European countries, and North America. Recombination analysis within the enterovirus B specie (59 serotypes) revealed eight recombination patterns in China at present, CVB4, CVB5, E30, CVB2, E11, HEV106, HEV85, and HEV75. E14, and E6 may act as recombinant donors in multiple regions. Comparison of temperature sensitivity revealed that temperature-insensitive strains have more amino acid substitutions in the RGD motif of the VP1 region, and the sites T283S, V284M, and R288K in the VP1 region may be related to the temperature tolerance of CVA9.

Keywords: coxsackievirus A9; evolutionary reconstruction; genotyping; recombination.

Publication types

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

MeSH terms

China / epidemiology
Enterovirus B, Human* / genetics
Evolution, Molecular
Genotype
Molecular Epidemiology
Nucleotides*
Phylogeny

Substances

Nucleotides