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.

口蹄疫（Foot-and-Mouth Disease, FMD）严重掣肘全球畜牧业的健康发展，而口蹄疫病毒（Foot-and-Mouth Disease Virus, FMDV）的致病机制尚未阐明，使得口蹄疫的防控与净化工作面临重重困难。糖酵解重塑被视为病毒感染的标志性特征之一，可为病毒组装与复制提供能量及前体物质。本研究从免疫代谢的视角出发，探究了口蹄疫病毒与宿主糖酵解过程之间的相互作用及其调控机制。研究发现，口蹄疫病毒感染会导致细胞外酸化率升高、乳酸堆积以及己糖激酶2（Hexokinase 2, HK2）表达水平上调。此外，在口蹄疫病毒感染过程中，己糖激酶2可增强糖酵解活性，并通过介导干扰素调节因子3/7（Interferon Regulatory Factor 3/7, IRF3/7）的自噬降解，拮抗宿主先天免疫应答，进而促进病毒复制。本研究结果证实口蹄疫病毒与宿主代谢过程密切相关，丰富了人们对糖酵解及己糖激酶2辅助病毒感染的认知，同时为进一步阐明口蹄疫病毒的致病机制提供了全新的研究思路。