Phylodynamic Characterization of an Ocular-Tropism Coxsackievirus A24 Variant

Abstract

Recent phylodynamic studies have focused on using tree topology patterns to elucidate interactions among the epidemiological, evolutionary, and demographic characteristics of infectious agents. However, because studies of viral phylodynamics tend to focus on epidemic outbreaks, tree topology signatures of tissue-tropism pathogens might not be clearly identified. Therefore, this study used a novel Bayesian evolutionary approach to analyze the A24 variant of coxsackievirus (CV-A24v), an ocular-tropism agent of acute hemorrhagic conjunctivitis. Analyses of the 915-nucleotide VP1 and 690-nt 3Dpol regions of 21 strains isolated in Taiwan and worldwide during 1985–2010 revealed a clear chronological trend in both the VP1 and 3Dpol phylogenetic trees: the emergence of a single dominant cluster in each outbreak. The VP1 sequences included three genotypes: GI (prototype), GIII (isolated 1985–1999), and GIV (isolated after 2000); no VP1 sequences from GII strains have been deposited in GenBank. Another five genotypes identified in the 3Dpol region had support values >0.9. Geographic and demographic transitions among CV-A24v clusters were clearly identified by Bayes algorithm. The transmission route was mapped from India to China and then to Taiwan, and each prevalent viral population declined before new clusters emerged. Notably, the VP1 and 3Dpol genes had high nucleotide sequence similarities (94.1% and 95.2%, respectively). The lack of co-circulating lineages and narrow tissue tropism affected the CV-A24v gene pool.

Coxsackievirus A24 Variant Associated with Acute Haemorrhagic Conjunctivitis Cases, French Guiana, 2017

“…In all the genomic regions, the isolates from French Guiana were closer to other CV-A24vs than to any other CV-A24 or any enterovirus of another type (data not shown). These observations are consistent with a continuous evolution of the genogroup IV CV-A24v strains through genetic drift with no intertypic recombination events with other EVs [17]. The absence of recombination events between these CV-A24vs and other EVs could be due to their peculiar tropism, which probably impedes genetic exchanges with other EVs that replicate mainly in the gut.…”

“…Our isolates fell into the CV-A24v genotype IV [16, 17], together with strains found worldwide in the 2000s and 2010s during AHC outbreaks (Fig. 1).…”

“…Within genotype IV, recent studies have defined 5 clusters of strains [17, 19]. These clusters consist of strains that segregate together temporally, with each cluster circulating for a few years.…”

Molecular epidemiology of acute hemorrhagic conjunctivitis caused by coxsackie A type 24 variant in China, 2004–2014

“…G3 includes six clusters of strains isolated beginning in 1985 in Asia, Africa and France30. G4 includes six clusters of strains that have been identified to date336. This study demonstrated that CA24v was the causative agent of AHC outbreak in China during 2004 to 2014.…”

Molecular evolution of coxsackievirus A24v in Cuba over 23-years, 1986–2009

“…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. Afterwards, CVA24v has been identified as the major causative agent of AHC outbreaks worldwide 3 – 5 . Currently, four genotypes of CVA24v have been described (I–IV), which have been responsible for major global epidemics of AHC 5 – 7 .…”