The multitaskers of the brain: Glial responses to viral infections and associated post-infectious neurologic sequelae

Many viral infections cause acute and chronic neurologic diseases which can lead to degeneration of cortical functions. While neurotropic viruses that gain access to the central nervous system (CNS) may induce brain injury directly via infection of neurons or their supporting cells, they also alter brain function via indirect neuroimmune mechanisms that may disrupt the blood-brain barrier (BBB), eliminate synapses, and generate neurotoxic astrocytes and microglia that prevent recovery of neuronal circuits. Non-neuroinvasive, neurovirulent viruses may also trigger aberrant responses in glial cells, including those that interfere with motor and sensory behaviors, encoding of memories and executive function. Increasing evidence from human and animal studies indicate that neuroprotective antiviral responses that amplify levels of innate immune molecules dysregulate normal neuroimmune processes, even in the absence of neuroinvasion, which may persist after virus is cleared. In this review, we discuss how select emerging and re-emerging RNA viruses induce neuroimmunologic responses that lead to dysfunction of higher order processes including visuospatial recognition, learning and memory, and motor control. Identifying therapeutic targets that return the neuroimmune system to homeostasis is critical for preventing virus-induced neurodegenerative disorders.