Comparative genomic analysis of coxsackievirus A6 strains of different clinical disease entities

PLoS One. 2012;7(12):e52432. doi: 10.1371/journal.pone.0052432. Epub 2012 Dec 26.

Abstract

Background: Studies regarding coxsackievirus A6 (CVA6) infection were limited. In Taiwan, outbreaks of CVA6 occurred in 2009 and 2010, respectively, but the clinical manifestations were markedly different. We conducted a study to compare the clinical features and genomic sequence between the two years.

Methodology/principal findings: In 2009 and 2010, 205 patients with coxsackievirus A6 (CVA6) infection were treated at Chang Gung Memorial Hospital. Detailed clinical features were obtained from 126 inpatients, 62 in 2009 and 64 in 2010. Between the inpatients in 2009 and 2010, no statistically significant difference was noted in terms of demographics, length of hospital stay and laboratory data. Significantly more patients in 2009 presented with herpangina (82%) while more patients in 2010 presented with hand-foot-mouth disease (HFMD; 67%) and skin rash beyond the typical sites for HFMD. Complete genomic sequences were determined and compared for three isolates from patients with herpangina in 2009 and three isolates from patients with HFMD in 2010. The complete sequences showed that 2009 and 2010 CVA6 isolates were indistinguishable by partial VP1 genes, but there were 5 unique nucleotide changes in 3' UTR, and 23 out of 2201 (1%) amino acids were different. 2010 viruses underwent the largest number of amino acid changes in 3CD protein, which is the precursor of both 3C protease and 3D polymerase.

Conclusions: Since 2008 in Finland, outbreaks of HFMD due to CVA6 were noted internationally. CVA6 of different genetic background may cause different clinical manifestations such as herpangina and HFMD.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Capsid Proteins / genetics
  • Cell Line
  • Child, Preschool
  • Coxsackievirus Infections / virology*
  • Dogs
  • Enterovirus / genetics*
  • Enterovirus / isolation & purification
  • Enterovirus / physiology*
  • Female
  • Genomics*
  • Humans
  • Male
  • Sequence Analysis

Substances

  • Capsid Proteins

Grants and funding

This work was supported by the grants from Chang Gung Memorial Hospital. (CMRPG 470132, CMRPG320019, CMRPG371663 and CLRPG3B0041). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.