Dysregulated host lipid metabolism contributes to viral pathogenesis in the central nervous system with implications for therapy

Neurotropic viral infections represent an important and increasingly recognised component of the neuro-exposome, functioning as biological environmental exposures that interact with host metabolic systems to influence brain health. While viral neurotropism and immune-mediated mechanisms have been widely studied, the contribution of host lipid metabolism to viral replication, neuroinflammation, and neurodegeneration remains insufficiently integrated across disciplines. This scoping review aimed to synthesise current evidence on the interplay between host lipid metabolism and viral pathogenesis in the central nervous system, and to identify mechanistic pathways and translational opportunities relevant to neuro-exposome research. Following the PRISMA-ScR guidelines, a systematic search was conducted in PubMed, Embase, and Scopus for studies published between 2020 and 2025. Eligible in vitro, in vivo, and multi-omic studies examining lipidomic alterations associated with neurotropic viral infections were included and synthesised thematically. Across diverse viral families, convergent disruptions were identified in cholesterol homeostasis, fatty acid metabolism, sphingolipid signalling, lipid raft organisation, and ferroptosis-related pathways. These lipid alterations were consistently associated with enhanced viral entry and replication, blood–brain barrier dysfunction, chronic neuroinflammation, synaptic impairment, demyelination, and neurodegenerative processes, including Alzheimer’s disease-like pathology, particularly in genetically susceptible populations. The evidence supports dysregulation of host lipid metabolism as a unifying mechanism linking viral environmental exposures to adverse neurological outcomes. Integrating neurolipidomic pathways into neuro-exposome frameworks highlights opportunities for lipid-based biomarkers and metabolically targeted therapeutic strategies, advancing precision approaches to the prevention, diagnosis, and management of virus-associated neurological disorders.