Flaviviruses are a family of enveloped viruses with a positive-sense RNA genome, transmitted by arthropod vectors. These viruses are known for their broad cellular tropism leading to infection of multiple body systems, which can include the central nervous system. Neurologic effects of flavivirus infection can arise during both acute and post-acute infectious periods; however, the molecular and cellular mechanisms underlying post-acute sequelae are not fully understood. Here, we review recent studies that have examined molecular and cellular mechanisms that may contribute to neurologic sequelae following infection with the West Nile virus, Japanese encephalitis virus, Zika virus, dengue virus, and St. Louis encephalitis virus. Neuronal death, either from direct infection or due to the resultant inflammatory response, is a common mechanism by which flavivirus infection can lead to neurologic impairment. Other types of cellular damage, such as oxidative stress and DNA damage, appear to be more specific to certain viruses. This article aims to highlight mechanisms of cellular damage that are common across several flavivirus members and mechanisms that are more unique to specific members. Our goal is to inspire further research to improve understanding of this area in the hope of identifying treatment options for flavivirus-associated neurologic changes.
Keywords: DNA damage; Japanese encephalitis virus; St. Louis encephalitis virus; West Nile virus; Zika virus; apoptosis; dengue virus; flavivirus; microglia; neurons.