Jernej Jorgačevski

Astrocytes are increasingly recognized as important viral host cells in the central nervous system. These cells can produce relatively high quantities of new virions. In part, this can be attributed to the characteristics of astrocyte metabolism and its abundant and dynamic cytoskeleton network. Astrocytes are anatomically localized adjacent to interfaces between blood capillaries and brain parenchyma and between blood capillaries and brain ventricles. Moreover, astrocytes exhibit a larger membrane interface with the extracellular space than neurons. These properties, together with the expression of various and numerous viral entry receptors, a relatively high rate of endocytosis, and morphological plasticity of intracellular organelles, render astrocytes important target cells in neurotropic infections. In this review, we describe factors that mediate the high susceptibility of astrocytes to viral infection and replication, including the anatomic localization of astrocytes, morphology, expression of viral entry receptors, and various forms of autophagy.

Neuroinfections of the central nervous system (CNS) can be triggered by various pathogens. Viruses are the most widespread and have the potential to induce long-term neurologic symptoms with potentially lethal outcomes. In addition to directly affecting their host cells and inducing immediate changes in a plethora of cellular processes, viral infections of the CNS also trigger an intense immune response. Regulation of the innate immune response in the CNS depends not only on microglia, which are fundamental immune cells of the CNS, but also on astrocytes. These cells align blood vessels and ventricle cavities, and consequently, they are one of the first cell types to become infected after the virus breaches the CNS. Moreover, astrocytes are increasingly recognized as a potential viral reservoir in the CNS; therefore, the immune response initiated by the presence of intracellular virus particles may have a profound effect on cellular and tissue physiology and morphology. These changes should be addressed in terms of persisting infections because they may contribute to recurring neurologic sequelae. To date, infections of astrocytes with different viruses originating from genetically distinct families, including Flaviviridae, Coronaviridae, Retroviridae, Togaviridae, Paramyxoviridae, Picomaviridae, Rhabdoviridae, and Herpesviridae, have been confirmed. Astrocytes express a plethora of receptors that detect viral particles and trigger signaling cascades, leading to an innate immune response. In this review, we summarize the current knowledge on virus receptors that initiate the release of inflammatory cytokines from astrocytes and depict the involvement of astrocytes in immune functions of the CNS.