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PGC-1alpha mediates a metabolic host defense response in human airway epithelium during rhinovirus infections

ABSTRACT: Human rhinoviruses (HRV) are common cold viruses associated with exacerbations of lower airways diseases. Although viral induced epithelial damage mediates inflammation, the molecular mechanisms responsible for airway epithelial damage and dysfunction remain undefined. Using experimental HRV infection studies in humans and highly differentiated human bronchial epithelial cells grown at air-liquid interface (ALI), we examined the links between viral host defense, cellular metabolism, and epithelial barrier function. We observed that early HRV-C15 infection induced a transitory barrier-protective metabolic state characterized by glycolysis that ultimately becomes exhausted as the infection progresses and leads to cellular damage. Pharmacological promotion of glycolysis induced ROS-dependent upregulation of the mitochondrial metabolic regulator, peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha), thereby restoring epithelial barrier function, improving viral defense, and attenuating disease pathology. Therefore, PGC-1alpha regulates a metabolic pathway essential to host defense that can be therapeutically targeted to rescue airway epithelial barrier dysfunction and potentially prevent severe respiratory complications or secondary bacterial infections.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human) Viruses

TISSUE(S): Lung, Epithelial Cell

SUBMITTER: Antoine Dufour

LAB HEAD: Antoine Dufour

PROVIDER: PXD024591 | Pride | 2021-04-30

REPOSITORIES: Pride

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