Mechanistic role of lipid metabolism in foot-and-mouth disease virus (FMDV) replication

Foot-and-mouth disease (FMD) is a highly contagious animal disease caused by foot-and-mouth disease virus (FMDV), primarily affecting cloven-hoofed animals such as swine, cattle, and sheep. As a core metabolic pathway for maintaining cellular homeostasis, lipid metabolism is frequently hijacked by viruses via metabolic reprogramming mechanisms to support their infection cycle. Studies have demonstrated that positive-sense single-stranded RNA viruses can reshape the host cell membrane system and modulate the lipid metabolic network, thereby constructing a favorable microenvironment for their invasion and replication. However, the molecular mechanisms by which FMDV-also a positive-sense single-stranded RNA virus-promotes viral replication through the regulation of lipid metabolism remain incompletely elucidated. In this study, we found that inhibiting the key enzymes involved in the lipid metabolic pathway could significantly suppress FMDV proliferation. Exogenous supplementation of the downstream products catalyzed by these key enzymes notably restored FMDV replication, indicating that FMDV replication is dependent on lipids. Furthermore, we observed a significant upregulation in the protein expression of carnitine palmitoyltransferase 1A (CPT1A) in host cells following FMDV infection. Inhibition of this enzyme led to a marked reduction in FMDV replication, suggesting that FMDV may enhance the fatty acid β-oxidation pathway to supply energy for its replication. In conclusion, this study comprehensively verified the critical role of lipid metabolism in FMDV replication through multidimensional assays involving the administration of inhibitors targeting key enzymes in the lipid metabolic pathway. These findings provide novel theoretical insights for the development of antiviral drugs and the prevention and control of FMD.