Genetic Variation and Evolutionary Characteristics of Coxsackievirus B1: F3 Subtype Associated With Hand, Foot and Mouth Disease in China.
Coxsackievirus B1 (CV-B1) is primarily associated with meningitis but can also cause localized outbreaks of hand, foot, and mouth disease (HFMD). This study analyzed the genetic diversity of the VP1 gene in 39 strains of the CVB1 virus isolated from HFMD children across 15 provinces in China between 2010 and 2024, as well as 179 strains from 17 countries. Based on the average nucleotide difference of VP1 gene, we classified CVB1 virus into six genotypes A to F, Notably, genotype F is newly classified. Since 2010, genotype F guadually replaced genotype E as the dominant genotype in China and has further subdivided into three subtypes: F1, F2, and F3, with F3 being the most prevalent subtype in China currently. We specifically study the mild and severe cases within the F3 subtype. Temperature-sensitivity experiments revealed no differences between mild and severe cases of the F3 subtype, and they all belong to temperature-sensitive strains. Interestingly, we found that mild cases of the F3 subtype did not involve recombination, whereas all severe cases of the F3 subtype showed recombination with Coxsackievirus B4 (CVB4). CVB4 has consistently been the primary pathogen responsible for severe neonatal illnesses, suggesting that recombination between the F3 subtype and CVB4 may be associated with the development of severe HFMD. These findings provide fundamental scientific data for further investigation into the epidemiology and genetic characteristics of variants of Coxsackievirus B1 in China.