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.

Highlights

  • The coxsackievirus A24 variant (CV-A24v), an enterovirus (EV) C species of Picornaviridae, is an antigenic mutant of CV-A24

  • The CV-A24v isolates analyzed exhibited high sequence similarity with those recently reported in the literature [28, 29], which indicates that sequences for tissue-specific pathogens such as CV-A24v may be fixed by adaptation

  • To achieve a clear depiction of the evolution of CV-A24v, we performed VP1- and 3Dpol-based analyses in this ocular-tropism virus and reconstructed its phylodynamic history. In both the VP1 and 3Dpol regions, low sequence variation and the absence of recombination suggest that narrow tissue tropism may limit sequence variation

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Summary

Introduction

The coxsackievirus A24 variant (CV-A24v), an enterovirus (EV) C species of Picornaviridae, is an antigenic mutant of CV-A24. An ocular tropism results from the use of a sialylated glycoprotein as a cellular receptor [1], and CV-A24v is known to be a major causative agent of acute hemorrhagic conjunctivitis (AHC) with pandemic potential [2]. After the first report of an AHC outbreak caused by CV-A24v in Taiwan in 1985–1986, CV-A24v intermittently reappeared in 1988–1989, 1990–1991, 1994, 2000–2002, 2006–2007 and 2010. In the emergence period during the 1970s, CV-A24v was limited to Asia. The geographic expansion period in the 1980s was characterized by outbreaks in Asia, Central America, and North Africa and was followed by a quiescence period, which lasted a decade. CV-A24v re-emerged in the wide dispersal period after 2000 [3]. Since CV-A24v outbreaks occur periodically in tropical areas and involve large populations, the emergence of CV-A24v is a major public health concern, in densely populated areas. The most at-risk age group has shifted from adults (before 1999) to teenagers (after 2000) [5, 6], possibly due to technological changes such as sharing computing devices by multiple users

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