Journal Article

Phylodynamic and Epistatic Analysis of Coxsackievirus A24 and Its Variant

Chu, Pei-Huan, Ke, Guan-Ming, Chu, Pei-Yu, Ke, Liang-Yin, Cheng, Chia-Chi, Huang, Hui-Wen

2024

Overview

Coxsackievirus A24 (CV-A24) is a human enterovirus that causes acute flaccid paralysis. However, a Coxsackievirus A24 variant (CV-A24v) is the most common cause of eye infections. The causes of these variable pathogenicity and tissue tropism remain unclear. To elucidate the phylodynamics of CV-A24 and CV-A24v, we analyzed a dataset of 66 strains using Bayesian phylodynamic approach, along with detailed sequence variation and epistatic analyses. Six CV-A24 strains available in GenBank and 60 CV-A24v strains, including 11 Taiwanese strains, were included in this study. The results revealed striking differences between CV-A24 and CV-A24v exhibiting long terminal branches in the phylogenetic tree, respectively. CV-A24v presented distinct ladder-like clustering, indicating immune escape mechanisms. Notably, 10 genetic recombination events in the 3D regions were identified. Furthermore, 11 missense mutation signatures were detected to differentiate CV-A24 and CV-A24v; among these mutations, the F810Y substitution may significantly affect the secondary structure of the GH loop of VP1 and subsequently affect the epitopes of the capsid proteins. In conclusion, this study provides critical insights into the evolutionary dynamics and epidemiological characteristics of CV-A24 and CV-A24v, and highlights the differences in viral evolution and tissue tropism.

• Publisher: MDPI AG,MDPI
• Subject: Bayes Theorem / Bayesian analysis / Bayesian theory / capsid / Capsid Proteins - genetics / Comparative analysis / Coxsackievirus / Coxsackievirus A24 (CV-A24) / Coxsackievirus A24 variant (CV-A24v) / Coxsackievirus Infections - virology / Coxsackieviruses / data collection / Datasets / Enterovirus C, Human - classification / Enterovirus C, Human - genetics / Epidemiology / Epistasis / Epistasis, Genetic / Epitopes / eyes / Genetic aspects / genetic recombination / Genetic Variation / Genome, Viral / Genomes / Human enterovirus / Humans / Missense mutation / Mutation, Missense / Paralysis / Pathogenicity / phylodynamics / Phylogenetics / Phylogeny / Physiological aspects / Protein structure / Recombination, Genetic / Regression analysis / RNA polymerase / Secondary structure / sequence diversity / Taiwan - epidemiology / tissue tropism / Trends / Tropism / VP1 protein