W94 - Herpes Simplex Virus Type 1 Modulation of Neutral Lipid Metabolism in Dendritic Cells Affects the Function of These Cells

Herpes simplex virus type 1 is a prevalent human pathogen that causes lifelong infection by latently infecting neurons. HSV-1 also infects dendritic cells (DCs), affecting their viability, maturation profile and capacity to present viral antigens to T cells, thus impairing an effective immune response against this virus. On the other hand, lipid droplets (LDs) are neutral lipid-rich organelles mainly composed of triglycerides and cholesterol esters, a phospholipid monolayer and surrounded by proteins associated with neutral lipid metabolism, among others. LD functions are mainly related to energy reserve sources; however, LDs have also been associated with immune system regulation, wherein LD accumulation impairs the DCs antigen presentation to T cells. A recent study indicated that early HSV-1 infection induces LDs accumulation in astrocytes and epithelial cells, a process associated with an increase in the interferon antiviral response. We observed by confocal and transmission electron microscopy that HSV-1 induces LD accumulation in DCs. Moreover, RT-qPCR analyses indicate that HSV-1 regulates the expression of neutral lipid biogenesis-associated genes. Further, we determined that the inhibition of neutral lipid biogenesis pathways reduces HSV-1 plaque-forming units (PFU), a process associated with reduced LDs accumulation in infected-DCs. Moreover, the pharmacological inhibition of neutral lipid synthesis pathways recovered DC viability and increased MHC-I as well as MHC-II expression on the surface of DCs. Our results indicate that HSV-1 modulates neutral lipid biogenesis inducing LD accumulation and impacting DCs function.