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Use of Viral Entry Assays and Molecular Docking Analysis for the Identification of Antiviral Candidates against Coxsackievirus A16
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Molecular Epidemiology and Evolution of Coxsackievirus A14

Liheng Yu1, Qin Guo1, Haiyan Wei2

  • 1National Polio Laboratory, WHO WPRO Regional Polio Reference Laboratory, National Health Commission Key Laboratory for Biosecurity, National Health Commission Key Laboratory of Medical Virology, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.

Viruses
|December 23, 2023
PubMed

Insights

This study analyzes Coxsackievirus A14 (CVA14) evolution, revealing its genotypes, origin in 1942, and complex migration patterns. Findings fill gaps in understanding CVA14 epidemiology and its role in hand, foot, and mouth disease.

Area of Science:

  • Virology
  • Molecular Epidemiology
  • Phylodynamics

Background:

  • Increasing global prevalence of non-enterovirus 71 and non-coxsackievirus A16 in hand, foot, and mouth disease (HFMD) necessitates research into other enteroviruses.
  • Coxsackievirus A14 (CVA14), a member of the enterovirus A species, is epidemic globally, yet its evolutionary dynamics and recombination patterns remain poorly understood.
  • Limited molecular epidemiological data exists for CVA14, hindering comprehensive understanding of its global spread and genetic diversity.

Purpose of the Study:

  • To investigate the molecular epidemiological characteristics of Coxsackievirus A14 (CVA14) strains.
  • To determine the evolutionary dynamics, genetic diversity, and recombination patterns of CVA14.
  • To establish the phylogeography and estimate the origin of CVA14.

Main Methods:

  • Isolation and complete genome sequencing of 15 CVA14 strains from HFMD patients in mainland China (2009-2019).
  • Bioinformatic analysis of complete genome sequences and full-length VP1 coding regions from isolated strains and GenBank data.
  • Phylodynamic and phylogeographic analyses, including Bayesian skyline plots and recombination detection.

Main Results:

  • CVA14 strains were classified into seven genotypes (A-G) based on VP1 sequence divergence (>15%).
  • Phylodynamic analysis estimated the mean substitution rate at 5.35 × 10^-3 substitutions/site/year, with the most recent common ancestor (tMRCA) dating back to 1942 (1930-1950).
  • Bayesian skyline plots indicated population size fluctuations since 2004, with identified migration routes globally and within China. Four recombination patterns were observed, with CVA2, CVA4, CVA6, CVA8, and CVA12 potentially acting as recombinant donors.

Conclusions:

  • This study provides the first comprehensive molecular epidemiological analysis of CVA14, filling a critical knowledge gap.
  • The findings enrich the global CVA14 sequence database and establish a foundation for future research into its worldwide epidemiology.
  • Understanding CVA14's genetic diversity, evolutionary history, and recombination is crucial for managing HFMD outbreaks.
Keywords:
coxsackievirus A14phylodynamic analysisrecombination

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