HSV-1-Driven Lipid Metabolic Reprogramming and Lipid Droplet Accumulation in Macrophages Impair Antiviral Immunity.

PURPOSE: Herpes simplex virus type 1 (HSV-1) is a continuous health challenge, infecting 64% of the global population under the age of 50 years. Macrophages play a critical role in antiviral immunity by integrating metabolic status with effector functions. This study aimed to investigate how HSV-1 infection reshapes macrophage metabolism and to elucidate the consequent effects on innate and adaptive immune regulation.

METHODS

We isolated bone marrow-derived macrophages (BMDMs) and assessed HSV-1-induced metabolic alterations using transcriptome sequencing, metabolomic profiling, and flow cytometry. We further used pharmacological inhibitors targeting key metabolic enzymes and co-culture system to evaluate macrophage functions. The main findings were validated in an in vivo mouse model of HSV-1 infection.

RESULTS

We found that HSV-1 infection induced marked lipid droplet (LD) accumulation in BMDMs. Pharmacological inhibition of diacylglycerol acyltransferase 2 (DGAT2) significantly reduced LD accumulation, limited viral replication, and enhanced the antiviral effector functions of macrophages.

CONCLUSIONS

Overall, our findings suggest that HSV-1-induced LD accumulation exerts a negative regulatory effect on macrophage immune function.