Molecular evolution of coxsackievirus A24v in Cuba over 23-years, 1986\u20132009

Magilé C Fonseca,Luis Morier,Luis A García-González,Mario Pupo-Meriño,Sonia Resik,Heléne Norder,Luis Sarmiento,Lai Heng Hung,Mayra Muné,Hermis Rodríguez

doi:10.1038/s41598-020-70436-w

Abstract

Coxsackievirus A24 variant (CVA24v) is a major causative agent of acute hemorrhagic conjunctivitis outbreaks worldwide, yet the evolutionary and transmission dynamics of the virus remain unclear. To address this, we analyzed and compared the 3C and partial VP1 gene regions of CVA24v isolates obtained from five outbreaks in Cuba between 1986 and 2009 and strains isolated worldwide. Here we show that Cuban strains were homologous to those isolated in Africa, the Americas and Asia during the same time period. Two genotypes of CVA24v (GIII and GIV) were repeatedly introduced into Cuba and they arose about two years before the epidemic was detected. The two genotypes co-evolved with a population size that is stable over time. However, nucleotide substitution rates peaked during pandemics with 4.39 × 10−3 and 5.80 × 10−3 substitutions per site per year for the 3C and VP1 region, respectively. The phylogeographic analysis identified 25 and 19 viral transmission routes based on 3C and VP1 regions, respectively. Pandemic viruses usually originated in Asia, and both China and Brazil were the major hub for the global dispersal of the virus. Together, these data provide novel insight into the epidemiological dynamics of this virus and possibly other pandemic viruses.

Highlights

Coxsackievirus A24 variant (CVA24v) is a major causative agent of acute hemorrhagic conjunctivitis outbreaks worldwide, yet the evolutionary and transmission dynamics of the virus remain unclear
This study identified that each epidemic of acute hemorrhagic conjunctivitis (AHC) in Cuba was caused by a genetically distinct CVA24v strain, and that the epidemics strains had emerged a few years before they gave rise to new epidemics
We demonstrated a sequential development of the CVA24v genotypes, each involved in pandemics, similar to what has been shown for other viruses causing major outbreaks or global spread such as influenza A virus, HIV and EV-D6833,34

Summary

Introduction

Coxsackievirus A24 variant (CVA24v) is a major causative agent of acute hemorrhagic conjunctivitis outbreaks worldwide, yet the evolutionary and transmission dynamics of the virus remain unclear. Pandemic viruses usually originated in Asia, and both China and Brazil were the major hub for the global dispersal of the virus. Coxsackievirus A24v (CVA24v), an antigenic variant of the CVA24 strain (member of species Enterovirus C), was first isolated from an outbreak of acute hemorrhagic conjunctivitis (AHC) in Singapore in 1970. Several studies have investigated the genetic diversity and molecular evolution of CVA24v strains during periods varying from 4 to 20 years[5,6,7]. The second nationwide outbreak occurred in 1992–1993 with 90,884 c ases[12,13] It is still unclear how the virus emerged in 1993 because there is no published data on possible AHC outbreaks in the Caribbean islands during this period. There were only few reported AHC outbreaks around the world during the early 1990s, those reported occurred in Asia and Africa[14,15,16]

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Conclusion