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Updated: Sep 3, 2026
Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
Published on: October 7, 2011
Enterovirus A71 and coxsackievirus A16 show different replication kinetics in human neuronal and non-neuronal cell
Thinesshwary Yogarajah1, Kien Chai Ong2, David Perera3
1Department of Pathology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
Insights
Enterovirus A71 (EV-A71) causes more severe hand, foot, and mouth disease (HFMD) neurological complications than coxsackievirus A16 (CV-A16) due to EV-A71
Area of Science:
- Virology
- Neuroscience
- Infectious Diseases
Background:
- Enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) are common causes of hand, foot, and mouth disease (HFMD).
- EV-A71 infections are frequently associated with severe neurological complications, unlike CV-A16 infections.
Purpose of the Study:
- To investigate the differential susceptibility of neuronal cells to EV-A71 and CV-A16.
- To compare the infection, replication, and spread of EV-A71 and CV-A16 in neuronal (SK-N-SH) and non-neuronal (RD) cell lines.
Main Methods:
- Comparative analysis of EV-A71 and CV-A16 infection, replication, and cell death in SK-N-SH and RD cells.
- Assessment of viral replication in cells transfected with viral RNA to evaluate entry-independent factors.
- Evaluation of cell-type specific viral replication and spread.
Main Results:
- CV-A16 exhibited significantly lower replication and induced less necrotic cell death in SK-N-SH neuronal cells compared to EV-A71.
- Similar proportions of infected cells and viral RNA transfection results indicated that receptor availability was not the primary factor for CV-A16's reduced replication.
- Both viruses replicated similarly in RD cells, suggesting cell type-specific restrictions on viral replication and spread.
Conclusions:
- Cell type-specific restrictions influence EV-A71 and CV-A16 replication, with SK-N-SH cells showing reduced CV-A16 growth.
- The lower replication and cell death caused by CV-A16 in neuronal cells align with its lower prevalence of neurotropism in HFMD outbreaks.
- Further in vivo studies and strain comparisons are necessary to validate these findings.
Abstract:
Enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) are closely related enteroviruses that cause hand, foot and mouth disease (HFMD) in children. Serious neurological complications almost always occur in EV-A71 infection, but are rare in CV-A16 infection. Based on the hypothesis that this may be because EV-A71 infects neuronal cells more easily than CV-A16, we compared virus infection, replication and spread of EV-A71 and CV-A16 in SK-N-SH cells. We found that CV-A16 invariably showed significantly lower replication and caused less necrotic cell death in SK-N-SH cells, compared with EV-A71. This was not due to a lower proportion of CV-A16-infected cells, since both viruses showed similar proportions of infected cells at all time points analyzed. Furthermore, reduced replication of CV-A16 in SK-N-SH cells does not appear to be due to limited viral receptor availability, which might limit viral entry, because experiments with viral RNA-transfected cells showed the same results as for live virus infections. On the other hand, no differences were observed between EV-A71 and CV-A16 in RD cells and results were generally similar in RD cells for both viruses. Taken together, our findings suggest that the poor growth of CV-A16 and EV-A71in SK-N-SH cells, compared with RD cells, may be due to cell type-specific restrictions on viral replication and spread. Furthermore, the lower viral replication and necrotic cell death in CV-A16-infected SK-N-SH cells, compared with EV-A71-infected SK-N-SH cells, is consistent with the lower prevalence of neurotropism observed in CV-A16-associated HFMD outbreaks. Nonetheless, in vivo data and more extensive comparisons of different viral strains are essential to confirm our findings.
