Lipid Droplets and Viruses: A Dynamic Battlefield of Cellular Resources

Lipid droplets (LDs) are evolutionarily highly conserved dynamic organelles. In addition to their canonical roles in energy homeostasis, membrane biosynthesis, and lipid signaling, accumulating evidence highlights their critical involvement in viral pathogenesis. As obligate intracellular parasites, viruses are entirely dependent on their host's cellular machinery. To replicate, they must hijack LDs to obtain essential lipids and energy, which are critical for assembling viral replication complexes and producing new virions. However, host cells do not passively accept viral invasion. Recent evidence demonstrates that pathogen infection triggers the innate immune response of host cells. This response, in turn, rewires lipid metabolism to drive the formation of new LDs. These newly formed LDs are characterized by surfaces enriched with immune proteins. These specialized lipid droplets serve as defensive structures that combat pathogen invasion through both direct and indirect mechanisms. This article provides a systematic review of the dual roles of LDs in viral infection: on the one hand, LDs are hijacked by viruses to facilitate their replication; on the other hand, they serve as central hubs in innate immunity, participating in host cell antiviral defense mechanisms. These findings lend substantial support to the hypothesis that " LDs constitute critical components of innate immunity", while offering novel perspectives for understanding virus-host interactions. Future investigations should focus on elucidating the specific molecular mechanisms through which LDs mediate immune regulation, and explore innovative antiviral therapeutic strategies through targeted modulation of LD metabolism.