How viral infections cause neuronal dysfunction: a focus on the role of microglia and astrocytes

In recent decades, a number of infectious viruses have emerged from wildlife or reemerged that pose a serious threat to global health and economies worldwide. Although many of these viruses have a specific target tissue, neurotropic viruses have evolved mechanisms to exploit weaknesses in immune defenses that eventually allow them to reach and infect cells of the central nervous system (CNS). Once in the CNS, these viruses can cause severe neuronal damage, sometimes with long-lasting, life-threatening consequences. Remarkably, the ability to enter the CNS and cause neuronal infection does not appear to determine whether a viral strain causes neurological complications. The cellular mechanisms underlying the neurological consequences of viral infection are not fully understood, but they involve neuroimmune interactions that have so far focused mainly on microglia. As the major immune cells in the brain, reactive microglia play a central role in neuroinflammation by responding directly or indirectly to viruses. Chronic reactivity of microglia leads to functions that are distinct from their beneficial roles under physiological conditions and may result in neuronal damage that contributes to the pathogenesis of various neurological diseases. However, there is increasing evidence that reactive astrocytes also play an important role in the response to viruses. In this review article, we summarize the recent contributions of microglia and astrocytes to the neurological impairments caused by viral infections. By expanding knowledge in this area, therapeutic approaches targeting immunological pathways may reduce the incidence of neurological and neurodegenerative disorders and increase the therapeutic window for neural protection.