Polyamines as Gatekeepers of Virus Replication and Central Nervous System Homeostasis

Polyamines are small, positively charged molecules essential for fundamental cellular processes, including transcription, translation, and membrane fluidity. In the central nervous system (CNS), these molecules serve as homeostatic gatekeepers by modulating neuroreceptors like NMDA and supporting autophagic clearance. While basal polyamine levels are necessary for proper neuronal differentiation and memory formation, their dysregulation is a hallmark of neurodegenerative pathologies such as Alzheimer's and Parkinson's diseases. Neurotropic viruses, including poliovirus, Zika virus, and human cytomegalovirus are significant human pathogens that rely on cellular metabolites for their replication, including polyamines. These pathogens exploit polyamines at multiple stages of their life cycles, relying on them for virion stability, cellular attachment, and the stimulation of viral enzyme activity. Notably, diverse viral families share this dependence, making polyamine biosynthesis a prime target for broad-spectrum antiviral therapies. This review covers the current understanding of polyamine metabolism in virus infection and CNS health and disease, as well as considering antiviral therapies targeting host polyamines to limit neurotropic virus infection.