Genomic Epidemiology and Transmission Dynamics of Global Coxsackievirus B4
Jinbo Xiao,
Jianxing Wang,
Huanhuan Lu,
Yang Song,
Dapeng Sun,
Zhenzhi Han,
Jichen Li,
Qian Yang,
Dongmei Yan,
Shuangli Zhu,
Yaowen Pei,
Xianjun Wang,
Wenbo Xu,
Yong Zhang
Affiliations
Jinbo Xiao
WHO WPRO Regional Polio Reference Laboratory, National Laboratory for Poliomyelitis and National Health Commission Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
Jianxing Wang
Shandong Center for Disease Control and Prevention, Jinan 250014, China
Huanhuan Lu
WHO WPRO Regional Polio Reference Laboratory, National Laboratory for Poliomyelitis and National Health Commission Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
Yang Song
WHO WPRO Regional Polio Reference Laboratory, National Laboratory for Poliomyelitis and National Health Commission Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
Dapeng Sun
Shandong Center for Disease Control and Prevention, Jinan 250014, China
Zhenzhi Han
Laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, Beijing 102206, China
Jichen Li
WHO WPRO Regional Polio Reference Laboratory, National Laboratory for Poliomyelitis and National Health Commission Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
Qian Yang
WHO WPRO Regional Polio Reference Laboratory, National Laboratory for Poliomyelitis and National Health Commission Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
Dongmei Yan
WHO WPRO Regional Polio Reference Laboratory, National Laboratory for Poliomyelitis and National Health Commission Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
Shuangli Zhu
WHO WPRO Regional Polio Reference Laboratory, National Laboratory for Poliomyelitis and National Health Commission Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
Yaowen Pei
Shandong Center for Disease Control and Prevention, Jinan 250014, China
Xianjun Wang
Shandong Center for Disease Control and Prevention, Jinan 250014, China
Wenbo Xu
WHO WPRO Regional Polio Reference Laboratory, National Laboratory for Poliomyelitis and National Health Commission Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
Yong Zhang
WHO WPRO Regional Polio Reference Laboratory, National Laboratory for Poliomyelitis and National Health Commission Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
The aim of this study was to determine the global genetic diversity and transmission dynamics of coxsackievirus B4 (CVB4) and to propose future directions for disease surveillance. Next-generation sequencing was performed to obtain the complete genome sequence of CVB4, and the genetic diversity and transmission dynamics of CVB4 worldwide were analyzed using bioinformatics methods such as phylogenetic analysis, evolutionary dynamics, and phylogeographic analysis. Forty complete genomes of CVB4 were identified from asymptomatic infected individuals and hand, foot, and mouth disease (HFMD) patients. Frequent recombination between CVB4 and EV-B multiple serotypes in the 3Dpol region was found and formed 12 recombinant patterns (A-L). Among these, the CVB4 isolated from asymptomatic infected persons and HFMD patients belonged to lineages H and I, respectively. Transmission dynamics analysis based on the VP1 region revealed that CVB4 epidemics in countries outside China were dominated by the D genotype, whereas the E genotype was dominant in China, and both genotypes evolved at a rate of > 6.50 × 10−3 substitutions/site/year. CVB4 spreads through the population unseen, with the risk of disease outbreaks persisting as susceptible individuals accumulate. Our findings add to publicly available CVB4 genomic sequence data and deepen our understanding of CVB4 molecular epidemiology.
