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Use of Viral Entry Assays and Molecular Docking Analysis for the Identification of Antiviral Candidates against Coxsackievirus A16
Published on: July 15, 2019
Molecular epidemiology and the evolution of human coxsackievirus A6
Jiratchaya Puenpa1, Sompong Vongpunsawad1, Riikka Österback2,3
1Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Insights
Coxsackievirus A6 (CV-A6) evolution drives hand, foot, and mouth disease (HFMD) outbreaks through novel recombinant forms. These recombinant forms have become widespread globally in recent years.
Area of Science:
- Virology
- Molecular Epidemiology
- Public Health
Background:
- Coxsackievirus A6 (CV-A6) is a primary cause of hand, foot, and mouth disease (HFMD) outbreaks.
- Recent HFMD epidemics are linked to CV-A6's evolutionary dynamics and the emergence of new recombinant forms (RFs).
Purpose of the Study:
- To investigate the evolutionary mechanisms and genetic diversity of CV-A6.
- To analyze the emergence and spread of CV-A6 recombinant forms.
Main Methods:
- Genotyping of VP1 capsid and 3Dpol genes from 151 CV-A6 variants collected in Europe and Asia (2013-2014).
- Bayesian phylogenetic analysis to reconstruct evolutionary relationships.
- Identification of recombination breakpoints in full-length genomes.
Main Results:
- A strong correlation was observed between CV-A6 genome recombination and sequence divergence.
- An estimated substitution rate of 8.1×10-3 substitutions/site/year and an RF half-life of 3.1 years were determined.
- Thirty-nine full-length genomes revealed recombination breakpoints between 2A-2C and 5' UTRs, with new RF groups (RF-E, -F, -H, -J, -K) originating from a common ancestor (RF-A).
Conclusions:
- The emergence and widespread dissemination of novel CV-A6 recombination groups in Europe and Asia within the last 8 years.
- CV-A6's ongoing evolution and recombination are key drivers of HFMD epidemiology.
Abstract:
Coxsackievirus A6 (CV-A6) is a major aetiologic agent for hand, foot and mouth disease (HFMD) in recent years. HFMD outbreaks associated with CV-A6 resulted from the evolutionary dynamics of CV-A6 and the appearance of novel recombinant forms (RFs). To examine this, 151 variants collected in 2013 and 2014 from Germany, Spain, Sweden, Denmark and Thailand were genotyped for the VP1 capsid and 3Dpol genes. Analysis of the VP1 gene showed an increasing correspondence between CV-A6 genome recombination and sequence divergence (estimated substitution rate of 8.1×10-3 substitutions site-1 year-1 and RF half-life of 3.1 years). Bayesian phylogenetic analysis showed that recent recombination groups (RF-E, -F, -H, -J and -K) shared a common ancestor (RF-A). Thirty-nine full-length genomes of different RFs revealed recombination breakpoints between the 2A-2C and the 5' UTRs. The emergence of new CV-A6 recombination groups has become widespread in Europe and Asia within the last 8 years.
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