FMDV activated glycolysis and hijacked HK2 to inhibit innate immunity and promote viral replication

FMD seriously restricts the healthy development of global animal husbandry, and the unclear pathogenic mechanism of FMDV leads to the difficulty of FMD prevention and purification. Glycolytic remodeling is considered as one of the hallmarks of viral infection, providing energy and precursors for viral assembly and replication. In this paper, the interaction and mechanism between FMDV and glycolysis were explored from the perspective of immune metabolism. We found that FMDV infection caused increased extracellular acidification rate, lactic acid accumulation, and high levels of HK2. In addition, during FMDV infection, HK2 enhanced glycolytic activity and mediates autophagy degradation of IRF3/7 to antagonize the innate immune response, thereby promoting viral replication. Our findings provide evidence supporting that FMDV is closely correlated with host metabolism, enriching the understanding that glycolysis and HK2 assist virus infection, and provide new ideas for further elucidating the pathogenic mechanism of FMDV.