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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
Phenotypic and genomic characterization of human coxsackievirus A16 strains with distinct virulence in mice
Jian-Feng Han1, Nan Yu2, Yu-Xian Pan2
1Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Insights
Two coxsackievirus A16 (CA16) strains from China showed different pathogenicity in mice despite similar lab growth. Genomic analysis revealed recombination with EV71, suggesting insights into enterovirus virulence.
Area of Science:
- Virology
- Molecular Biology
- Public Health
Background:
- Human coxsackievirus A16 (CA16) causes hand, foot, and mouth disease (HFMD) and severe neurological conditions in children, posing a significant public health concern in Asia.
- During a 2009 HFMD epidemic in Guangdong, China, two distinct CA16 strains were isolated.
Purpose of the Study:
- To compare the phenotypic and genomic characteristics of two clinical CA16 isolates.
- To identify potential virulence determinants and understand the evolutionary relationships of CA16 strains in China.
Main Methods:
- Isolation and characterization of CA16 strains.
- In vitro plaque morphology and growth property assessment.
- Pathogenicity testing in neonatal mice.
- Complete genome sequencing and phylogenetic analysis.
- Homologous recombination analysis using bootscanning.
Main Results:
- Both CA16 isolates exhibited similar in vitro plaque morphology and growth properties.
- The two strains displayed distinct pathogenicity in neonatal mice following intraperitoneal or intracranial injection.
- Phylogenetic analysis placed the Guangdong isolates within the B1b genotype, closely related to other recent Chinese CA16 strains.
- Homologous recombination between CA16 strains and the EV71 prototype strain BrCr was detected in non-structural gene regions and 3'-untranslated regions.
Conclusions:
- The study provides a detailed comparison of phenotypic and genomic features of two circulating CA16 strains.
- Potential amino acid residues contributing to CA16 virulence in a mouse model were predicted.
- Findings contribute to understanding the evolutionary dynamics of CA16 and warrant further research into enterovirus virulence mechanisms.
Abstract:
Human coxsackievirus A16 (CA16) infection results in hand, foot, and mouth disease (HFMD) along with other severe neurological diseases in children and poses an important public health threat in Asian countries. During an HFMD epidemic in 2009 in Guangdong, China, two CA16 strains (GD09/119 and GD09/24) were isolated and characterized. Although both strains were similar in plaque morphology and growth properties in vitro, the two isolates exhibited distinct pathogenicity in neonatal mice upon intraperitoneal or intracranial injection. Complete genome sequences of both CA16 strains were determined, and the possible virulence determinants were analyzed and predicted. Phylogenetic analysis revealed that these CA16 isolates from Guangdong belonged to the B1b genotype and were closely related to other recent CA16 strains isolated in mainland China. Similarity and bootscanning analyses of these CA16 strains detected homologous recombination with the EV71 prototype strain BrCr in the non-structural gene regions and the 3'-untranslated regions. Together, the phenotypic and genomic characterizations of the two clinical CA16 isolates circulating in China were compared in detail, and the potential amino acid residues responsible for CA16 virulence in mice were predicted. These findings will help explain the evolutionary relationship of the CA16 strains circulating in China, warranting future studies investigating enterovirus virulence.

