Key homeostasis providing cells in the central nervous system (CNS) are astrocytes, which belong to the class of cells known as atroglia, a highly heterogeneous type of neuroglia and a prominent element of the brain defence. Diseases evolve due to altered homeostatic state, associated with pathology-induced astroglia remodelling represented by reactive astrocytes, astroglial atrophy and astrodegeneration. These features are hallmarks of most infectious insults, mediated by bacteria, protozoa and viruses; they are also prominent in the systemic infection. The COVID-19 pandemic revived the focus into neurotropic viruses such as SARS-CoV2 (Coronaviridae) but also the Flaviviridae viruses including tick-borne encephalitis (TBEV) and Zika virus (ZIKV) causing the epidemic in South America prior to COVID-19. Astrocytes provide a key response to neurotropic infections in the CNS. Astrocytes form a parenchymal part of the blood–brain barrier, the site of virus entry into the CNS. Astrocytes exhibit aerobic glycolysis, a form of metabolism characteristic of highly morphologically plastic cells, like cancer cells, hence a suitable milieu for multiplication of infectious agent, including viral particles. However, why the protection afforded by astrocytes fails in some circumstances is an open question to be studied in the future.