1. Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis.
- Author
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Codo AC, Davanzo GG, Monteiro LB, de Souza GF, Muraro SP, Virgilio-da-Silva JV, Prodonoff JS, Carregari VC, de Biagi Junior CAO, Crunfli F, Jimenez Restrepo JL, Vendramini PH, Reis-de-Oliveira G, Bispo Dos Santos K, Toledo-Teixeira DA, Parise PL, Martini MC, Marques RE, Carmo HR, Borin A, Coimbra LD, Boldrini VO, Brunetti NS, Vieira AS, Mansour E, Ulaf RG, Bernardes AF, Nunes TA, Ribeiro LC, Palma AC, Agrela MV, Moretti ML, Sposito AC, Pereira FB, Velloso LA, Vinolo MAR, Damasio A, Proença-Módena JL, Carvalho RF, Mori MA, Martins-de-Souza D, Nakaya HI, Farias AS, and Moraes-Vieira PM
- Subjects
- Adult, COVID-19, Cell Line, Coronavirus Infections metabolism, Diabetes Complications metabolism, Diabetes Mellitus metabolism, Female, Glycolysis, Humans, Inflammation complications, Inflammation metabolism, Male, Middle Aged, Monocytes virology, Pandemics, Pneumonia, Viral metabolism, Reactive Oxygen Species metabolism, SARS-CoV-2, Signal Transduction, Betacoronavirus physiology, Blood Glucose metabolism, Coronavirus Infections complications, Diabetes Complications complications, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Monocytes metabolism, Pneumonia, Viral complications
- Abstract
COVID-19 can result in severe lung injury. It remained to be determined why diabetic individuals with uncontrolled glucose levels are more prone to develop the severe form of COVID-19. The molecular mechanism underlying SARS-CoV-2 infection and what determines the onset of the cytokine storm found in severe COVID-19 patients are unknown. Monocytes and macrophages are the most enriched immune cell types in the lungs of COVID-19 patients and appear to have a central role in the pathogenicity of the disease. These cells adapt their metabolism upon infection and become highly glycolytic, which facilitates SARS-CoV-2 replication. The infection triggers mitochondrial ROS production, which induces stabilization of hypoxia-inducible factor-1α (HIF-1α) and consequently promotes glycolysis. HIF-1α-induced changes in monocyte metabolism by SARS-CoV-2 infection directly inhibit T cell response and reduce epithelial cell survival. Targeting HIF-1ɑ may have great therapeutic potential for the development of novel drugs to treat COVID-19., Competing Interests: Declaration of Interests Authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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