Ex vivo study of neuroinvasive and neurotropic viruses: what is current and what is next

Numerous pathogens, including viruses, enter the central nervous system and cause neurological disorders, such as encephalitis. Viruses are the main etiologic agents of such neurological diseases, and some of them cause a high death toll worldwide. Our knowledge about neuroinvasive and encephalitogenic virus infections is still limited due to the relative inaccessibility of the brain. To mitigate this shortcoming, neural ex vivo models have been developed and turned out to be of paramount importance for understanding neuroinvasive and neurotropic viruses. In this review, we describe the major ex vivo models for the central nervous system, including neural cultures, brain organoids, and organotypic brain cultures. We highlight the key findings from these models and illustrate how these models inform on viral processes, including neurotropism, neuroinvasion, and neurovirulence. We discuss the limitations of ex vivo models, highlight ongoing progress, and outline next-generation ex vivo models for virus research at the interface of neuroscience and infectious diseases.