Coxsackievirus A16 in a 1-Day-Old Mouse Model of Central Nervous System Infection Shows Lower Neurovirulence than Enterovirus A71

Hooi, Y. T. and Ong, K. C. and Tan, S.H. and Perera, D. and Wong, K. T. (2020) Coxsackievirus A16 in a 1-Day-Old Mouse Model of Central Nervous System Infection Shows Lower Neurovirulence than Enterovirus A71. Journal of Comparative Pathology, 176. pp. 19-32.

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Abstract

Coxsackievirus A16 (CV-A16) and enterovirus A71 (EV-A71) are the major causes of hand, foot and mouthdisease in young children. Although less so with CV-A16, both viruses are associated with serious neurologicalsyndromes, but the differences between their central nervous system infections remain unclear. We conducted acomparative infection study using clinically-isolated CV-A16 and EV-A71 strains in a 1-day-old mouse modelto better understand the neuropathology and neurovirulence of the viruses. New serotype-specific probes for insitu hybridization were developed and validated to detect CV-A16 and EV-A71 RNA in infected tissues.Demonstration of CV-A16 virus antigens/RNA, mainly in the brainstem and spinal cord neurons, confirmedneurovirulence, but showed lower densities than in EV-A71 infected animals. A higher lethal dose50for CV-A16 suggested that CV-A16 is less neurovirulent. Focal virus antigens/RNA in the anterior horn white matterand adjacent efferent motor nerves suggested that neuroinvasion is possibly via retrograde axonal transport inperipheral motor nerves.

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