| First Author | Zhao C | Year | 2020 |
| Journal | Emerg Microbes Infect | Volume | 9 |
| Issue | 1 | Pages | 691-706 |
| PubMed ID | 32208814 | Mgi Jnum | J:290384 |
| Mgi Id | MGI:6435336 | Doi | 10.1080/22221751.2020.1742585 |
| Citation | Zhao C, et al. (2020) Deficiency of HIF-1alpha enhances influenza A virus replication by promoting autophagy in alveolar type II epithelial cells. Emerg Microbes Infect 9(1):691-706 |
| abstractText | Infection of influenza A virus (IAV) can trigger exaggerated pulmonary inflammation and induce acute lung injury (ALI). Limiting IAV replication and alleviation of pulmonary inflammation are two important therapeutic strategies for influenza virus infection. Recent studies have shown that hypoxia inducible factor-1alpha (HIF-1alpha) is an essential factor for the development and repair of ALI; however, the role and the underlying mechanisms of HIF-1alpha in IAV-induced ALI remain elusive. Here, we demonstrated that lung epithelial cell-specific Hif1alpha knockout mice infected with IAV developed more lung IAV replication and severe lung inflammation, which led to increased mortality compared to IAV-infected control mice. Moreover, knockdown of HIF1A in A549 cells (human alveolar type II epithelial cell line) promoted IAV replication in vitro. Mechanistically, knockdown of HIF1A reduced glycolysis by regulating transcription of glycolysis-related enzymes, which subsequently activated the AMPKalpha-ULK1 signalling pathway. Interestingly, AMPKalpha-ULK1 signalling promoted autophagy and augmented IAV replication. Taken together, deficiency of HIF-1alpha in lung epithelial cells reduces glycolysis and enhances AMPKalpha-ULK1-mediated autophagy, which finally facilitates IAV replication. These findings have deepened our understanding of the role of HIF-1alpha in regulating IAV replication and provided us novel therapeutic targets for combating influenza infection. |
