Back to Search
Start Over
Metabolic shifts modulate lung injury caused by infection with H1N1 influenza A virus.
- Source :
-
Virology [Virology] 2021 Jul; Vol. 559, pp. 111-119. Date of Electronic Publication: 2021 Apr 06. - Publication Year :
- 2021
-
Abstract
- Influenza A virus (IAV) infection alters lung epithelial cell metabolism in vitro by promoting a glycolytic shift. We hypothesized that this shift benefits the virus rather than the host and that inhibition of glycolysis would improve infection outcomes. A/WSN/33 IAV-inoculated C57BL/6 mice were treated daily from 1 day post-inoculation (d.p.i.) with 2-deoxy-d-glucose (2-DG) to inhibit glycolysis and with the pyruvate dehydrogenase kinase (PDK) inhibitor dichloroacetate (DCA) to promote flux through the TCA cycle. To block OXPHOS, mice were treated every other day from 1 d.p.i. with the Complex I inhibitor rotenone (ROT). 2-DG significantly decreased nocturnal activity, reduced respiratory exchange ratios, worsened hypoxemia, exacerbated lung dysfunction, and increased humoral inflammation at 6 d.p.i. DCA and ROT treatment normalized oxygenation and airway resistance and attenuated IAV-induced pulmonary edema, histopathology, and nitrotyrosine formation. None of the treatments altered viral replication. These data suggest that a shift to glycolysis is host-protective in influenza.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Female
Lung chemistry
Lung virology
Lung Injury prevention & control
Male
Mice
Mice, Inbred C57BL
Pyruvate Dehydrogenase Acetyl-Transferring Kinase antagonists & inhibitors
Tyrosine analogs & derivatives
Tyrosine analysis
Tyrosine metabolism
Virus Replication
Epithelial Cells metabolism
Glycolysis
Influenza A Virus, H1N1 Subtype pathogenicity
Lung metabolism
Lung Injury virology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0341
- Volume :
- 559
- Database :
- MEDLINE
- Journal :
- Virology
- Publication Type :
- Academic Journal
- Accession number :
- 33865074
- Full Text :
- https://doi.org/10.1016/j.virol.2021.03.008