Senecavirus A-induced glycolysis facilitates virus replication by promoting lactate production that attenuates the interaction between MAVS and RIG-I

• DOI: 10.1371/journal.ppat.1011371
• Publication Date: 2023-05-01T17:27:06Z
• Authors: Huizi Li; Cunhao Lin; Wenbao Qi; Zhenzhen Sun; Zhenxin Xie; Weixin Jia; Zhangyong Ning
• Keywords: Lactate dehydrogenase A; Hexokinase; Anaerobic glycolysis; SOD2

Senecavirus A (SVA)-induced porcine idiopathic vesicular disease has caused huge economic losses worldwide. Glucose metabolism in the host cell is essential for SVA proliferation; however, impact of virus on glucose cells and subsequent effects are still unknown. Here, glycolysis induced by shown to facilitate replication promoting lactate production, which then attenuates interaction between mitochondrial antiviral-signaling protein (MAVS) retinoic acid-inducible gene I (RIG-I). induces PK-15 cells, as indicated significantly increased expression hexokinase 2 (HK2), 6-phosphofructokinase (PFKM), pyruvate kinase M (PKM), phosphoglycerate 1 (PGK1), hypoxia-inducible factor-1 alpha (HIF-1α), superoxide dismutase-2 (SOD2) a dose-and replication-dependent manner, enhanced while reducing ATP generation. Overexpression PKM, PGK1, HIF-1α, PDK3 high concentrations promote replication, glycolytic inhibitors decrease it. Inhibition RLR signaling allowed better production attenuate MAVS RIG-I, regulatory effect was mainly via RIG-I signaling. infection mice PKM PGK1 tissues serum yields lactate. Mice treated with administered sodium showed elevated levels well suppressed induction interferon beta (IFNβ), IFNα, interferon-stimulated 15 (ISG15), interleukin 6 (IL-6). The inhibitory interferons lower oxamate low compared glucose, indicating that inhibited through vitro vivo . These results provide new perspective relationship innate immunity infection, suggesting or may be targets against virus.