Molecular evolutionary dynamics of Coxsackievirus A16 in Shenzhen, China, 2012-2022.

Objectives

To investigate the epidemiological and genetic characteristics of Coxsackievirus A16 (CVA16) associated with hand, foot and mouth disease (HFMD) in Shenzhen, China.

Methods

CVA16 was examined by a real-time RT-PCR method. Complete VP1 gene sequences of CVA16 strains were determined, and sequence analyses were performed using a series of bioinformatics programs.

Results

Of 6436 mild HFMD specimens collected between 2012 and 2022, 1395 (21.7%) were CVA16-positive, with annual detection rates ranging from 4.1% to 45.4% and peaking in 2018. Molecular phylogenetic analysis revealed the circulation of three CVA16 sub-genotypes (B1a, B1b and B3) in Shenzhen, China. The major sub-genotype was B1b from 2013 to 2019, while the sub-genotype B1a predominated in 2020-2022. Phylogenetic and sequence homology analyses suggested that re-emerging CVA16 B1a strains in Shenzhen originated from Vietnam and Thailand. The mean evolutionary rate of CVA16 strains circulating in Shenzhen was estimated at 3.604 × 10-3 substitutions per site per year. Distinct amino acid mutations in VP1 correlated with temporal shifts in Shenzhen's dominant CVA16 sub-genotypes: N14S/L23M for B1b, and T164K/V251I for the 2017-2022 re-emergent B1a.

Conclusion

In the post-EV-A71 vaccine era, CVA16 remains one of the major pathogens of HFMD in Shenzhen. Over the study period, the CVA16 sub-genotype in Shenzhen underwent a B1a→B1b→B1a turnover, which was associated with both imported lineages and local adaptive evolution. This study underscores the critical importance of continuous molecular surveillance for CVA16.