Neurotropic enteric viruses in animals: Comparative research, knowledge gaps, and the role of pathology

Enteric viruses are commonly associated with gastrointestinal diseases but have the capacity, with mostly unknown triggers, to invade the central nervous system (CNS). Neuropathogenic enteric viruses (NEV) that are able to cross or bypass the blood-brain barrier cause debilitating neurological inflammation and disease. The most notorious example of an enteric virus with potential neurotropism is poliovirus, a member of the Picornaviridae family. While poliovirus has been largely eradicated due to extensive vaccination programs, other nonpolio picornaviruses, as well as enteric viruses of other families, are increasingly recognized as causative agents in cases of encephalitis of unknown origin. In the past decade, cutting-edge high-throughput sequencing and bioinformatics strategies have revealed an increasing number of NEV associated with neurological diseases in various animal species. Information, especially pathogenesis studies, on animal enteric viruses with neurotropism is relatively scarce. This review provides an overview of known enteric viruses that invade the CNS, which should support our awareness of the potential etiologic agents and encourage a diagnostic plan that includes NEV. The many knowledge gaps in host susceptibility and viral pathogenesis along the gut-brain axis would benefit from increased discovery efforts and a deeper understanding of the pathogenesis and potential of enteric viruses affecting the nervous system of animals. Crossing of species barriers is common among enteric viruses, so a one-health approach to increase awareness of animal and human NEV would contribute to effective strategies to monitor, manage, and contain emerging zoonotic outbreaks.