Ex vivo study of neuroinvasive and neurotropic viruses: what's current and what's next.

Numerous pathogens can enter the central nervous system and cause neurological disorders such as encephalitis. Among them, viruses are the main etiologic agent and cause a high death toll worldwide. However, knowledge about neuroinvasive and encephalitogenic virus infection, and in particular early stages, is still limited due to the relative inaccessibility of the brain. Neural ex vivo models have been of paramount importance for studying these infections and mimicking what takes place in vivo. In this review, we summarize the characteristics of the main ex vivo models of the central nervous system (neural cultures, brain organoids, and organotypic brain cultures) and highlight key findings made with them regarding the characterization of the neuroinvasion, neurotropism, and neurovirulence of these viruses. We discuss the limitations of such models, improvements that are in progress and finally what the next generations of ex vivo models will look like, with an emphasis on the interest for virology research to implement neuroscience techniques in these models to better decipher neuroinfections at the molecular, cellular, neural network, and organ scales, which is still sorely lacking today.