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

• Published in: Journal of comparative pathology Vol. 176; pp. 19 - 32
• Main Authors: Hooi, Y.T., Ong, K.C., Tan, S.H., Perera, D., Wong, K.T.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2020
• Subjects: Animals; Animals, Newborn; Central Nervous System Infections - virology; coxsackievirus A16; Coxsackievirus Infections - virology; Disease Models, Animal; Enterovirus A, Human - pathogenicity; enterovirus A71; Mice; mouse model; neurovirulence; Virulence; coxsackievirus A16; enterovirus A71; mouse model; neurovirulence
• ISSN: 0021-9975; 1532-3129
• DOI: 10.1016/j.jcpa.2020.02.001

Coxsackievirus A16 (CV-A16) and enterovirus A71 (EV-A71) are the major causes of hand, foot and mouth disease in young children. Although less so with CV-A16, both viruses are associated with serious neurological syndromes, but the differences between their central nervous system infections remain unclear. We conducted a comparative infection study using clinically-isolated CV-A16 and EV-A71 strains in a 1-day-old mouse model to better understand the neuropathology and neurovirulence of the viruses. New serotype-specific probes for in situ 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, confirmed neurovirulence, but showed lower densities than in EV-A71 infected animals. A higher lethal dose50 for CV-A16 suggested that CV-A16 is less neurovirulent. Focal virus antigens/RNA in the anterior horn white matter and adjacent efferent motor nerves suggested that neuroinvasion is possibly via retrograde axonal transport in peripheral motor nerves.