Rotavirus hijacks  host gluconeogenesis-related signaling pathway to promote self-replication in Caco-2 cells

Abstract

Viruses have evolved mechanisms to usurp the host's metabolic resources for their own biosynthesis and replication, but host's glucose metabolism change after rotavirus (RV) stress remains unclear. The metabolic profile and differential gluconeogenesis analysis was performed by gas chromatography-mass spectroscopy on RV-infected cells.47 potential differential metabolites were identified to verify glycolytic/gluconeogenesis pathway after RV infection. Glucose consumption and key enzymes of gluconeogenesis (glucose 6-phosphatase (G-6-pase) and phosphoenolpyruvate carboxylase (PEPCK)) were further examined by glucose oxidase-peroxidase method and enzyme linked immunosorbent assay. We found the impairment of glucose consumption, G-6-pase and PEPCK activities which promote gluconeogenesis, were tested in RV infected Caco-2 cells. By Western blot analysis, further studies detected the downregulation expression level of SIK2, which was affected by its upstream proteins of downregulated PDK1, AKT and upregulation p-JNK, and as a consequence influenced the function of gluconeogenesis. In short, RV infection altered the glucose consumption in infectious Caco-2 cells and activated the host cellular gluconeogenesis, which was hijacked through p-JNK-PDK1-AKT-SIK2 signaling pathway for its proliferation and replication with accelerating non-sugar substances conversion into glucose.