Coxsackievirus B4: a Undervalued Pathogen that Associated with Hand, Foot and Mouth Disease Outbreak
Abstract Objectives: This study was conducted to discover the causes of Coxsackievirus B4 (CVB4) -induced hand, foot, and mouth disease (HFMD) outbreaks and its evolutionary characteristics.Methods: In this study, we sequenced isolates obtained during the outbreak for comparative analyses with previously sequenced strains. Phylogenetic analysis and evolutionary dynamics were performed to illustrate the genetic characteristics of CVB4 in China and worldwide.Results: The nucleotide sequence of CVB4 isolated during the outbreak in 2011 was more similar to that of CVB4 isolated in Shandong Province, China in 2010 (95.7–99.4%) than to other CVB4 isolated in China (90.9–98.8%). A phylogenetic analysis showed that CVB4 originated from a common ancestor in Shandong. CVB4 strains isolated worldwide could be classified into genotypes A–E according to the VP1 region. All CVB4 strains in China belonged to genotype E. The global population diversity of CVB4 fluctuated substantially over time, and CVB4 isolated from China accounted for a significant increase in diversity of CVB4. The average nucleotide substitution rate in VP1 of Chinese CVB4 (5.20 × 10-3 substitutions/site/year) was slightly higher than that of global CVB4 (4.82 × 10-3 substitutions/site/year). Conclusions: These findings explain both the 2011 outbreak and a global increase in CVB4 diversity. In addition to improving our understanding of a major outbreak, these findings provide a basis for the development of surveillance strategies.