Neuroinvasion via Peripheral Nerves in Epidemic Viral Encephalitis Caused by Enterovirus, Orthoflavivirus and SARS-Coronavirus

Pathogens invade the central nervous system (CNS) and cause infections either through the haematogenous route or via peripheral nerves. Neuroinvasion via peripheral nerves, involving spinal or cranial somatic nerves, is well-established for certain viral encephalitides such as rabies, herpes simplex encephalitis, and poliomyelitis. Advances in understanding emerging and re-emerging viruses that cause epidemic CNS infections have highlighted the growing importance of peripheral nerve pathways in viral neuroinvasion. This review focuses on epidemic viral encephalitides caused by three groups of RNA viruses, viz., enteroviruses (enterovirus A71 and enterovirus D68), orthoflaviviruses (West Nile virus and Japanese encephalitis virus), and severe acute respiratory syndrome coronaviruses (mainly severe acute respiratory coronavirus-2). We examine evidence supporting the hypothesis that peripheral nerve viral transmission may play an increasingly significant if not more critical role than the haematogenous route in neuroinvasion.