期刊
VIROLOGY
卷 559, 期 -, 页码 111-119出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2021.03.008
关键词
Acute respiratory distress syndrome; Metabolism; Nitrotyrosine; Oxidative phosphorylation
类别
资金
- C. Glenn Barber Fund
- National Heart Lung and Blood Institute at the National Institutes of Health [R01-HL137090, R01-HL138738]
This study found that inhibiting glycolysis worsens outcomes of influenza infection, while promoting TCA cycle flux and inhibiting OXPHOS can mitigate the effects of the virus. These findings suggest that a shift to glycolysis may be host-protective in influenza.
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.
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