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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
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Intertypic Recombination Between Coxsackievirus A16 and Enterovirus A71 Structural and Non-Structural Genes Modulates
Hooi Yee Chang1, Han Kang Tee2, Kien Chai Ong3
1Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia.
Vaccines
|October 28, 2025
Summary
Recombination between enterovirus A71 (EV-A71) and coxsackievirus A16 (CVA16) impacts hand, foot, and mouth disease virulence. A chimera virus showed potential as a bivalent vaccine against both EV-A71 and CVA16.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Enterovirus A71 (EV-A71) and coxsackievirus A16 (CVA16) are key causes of hand, foot, and mouth disease (HFMD).
- These viruses co-circulate and can recombine, but the impact of recombinants on viral properties is not fully understood.
- Recombination often involves non-structural genes, leaving the role of structural genes in virulence and immune response unclear.
Purpose of the Study:
- To investigate the influence of EV-A71 and CVA16 genetic recombination on viral replication, virulence, and immunogenicity.
- To identify specific viral genetic determinants responsible for virulence and pathogenesis.
- To evaluate the potential of chimeric viruses as vaccine candidates.
Main Methods:
- Construction of four chimeric viruses (Chi-CCE, Chi-ECE, Chi-EEC, Chi-CEC) by exchanging 5'UTR, P1, P2, and P3 genes between CVA16 and EV-A71.
- Assessment of viral replication and cytopathic effects in cell culture (rhabdomyosarcoma cells).
- Evaluation of in vivo virulence and protection efficacy in a newborn BALB/c mouse model.
Main Results:
- All chimeric viruses replicated more efficiently than CVA16.
- Chimeric viruses were generally avirulent in vivo, except for Chi-CCE and CVA16, which demonstrated high virulence in newborn mice.
- The 5'UTR and capsid P1 genes of CVA16 were identified as critical determinants of virulence.
- Elevated IL-10 levels suggested immune modulation by the viruses.
- Inactivated Chi-CCE provided complete protection against lethal CVA16 and EV-A71 challenge.
Conclusions:
- Genetic recombination between CVA16 and EV-A71 significantly affects viral virulence and vaccine efficacy.
- The CVA16 5'UTR and P1 genes play a crucial role in determining virulence.
- The chimeric virus Chi-CCE holds promise as a candidate for a bivalent vaccine against HFMD caused by EV-A71 and CVA16.
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