TY - JOUR TI - PGC-1α mediates a metabolic host defense response in human airway epithelium during rhinovirus infections AU - Michi, Aubrey N. AU - Yipp, Bryan G. AU - Dufour, Antoine AU - Lopes, Fernando AU - Proud, David T2 - Nature Communications AB - 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 highly differentiated human bronchial epithelial cells grown at air-liquid interface (ALI), we examine the links between viral host defense, cellular metabolism, and epithelial barrier function. We observe that early HRV-C15 infection induces 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 induces ROS-dependent upregulation of the mitochondrial metabolic regulator, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), thereby restoring epithelial barrier function, improving viral defense, and attenuating disease pathology. Therefore, PGC-1α 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. DA - 2021/06/16/ PY - 2021 DO - 10.1038/s41467-021-23925-z DP - www.nature.com VL - 12 IS - 1 SP - 3669 LA - en SN - 2041-1723 UR - https://www.nature.com/articles/s41467-021-23925-z Y2 - 2021/06/16/17:30:30 ER -