Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis
OPEN Cell metabolism | 23 Jul 2020
AC Codo, GG Davanzo, LB Monteiro, GF de Souza, SP Muraro, JV Virgilio-da-Silva, JS Prodonoff, VC Carregari, CAO de Biagi Junior, F Crunfli, JL Jimenez Restrepo, PH Vendramini, G Reis-de-Oliveira, K Bispo Dos Santos, DA Toledo-Teixeira, PL Parise, MC Martini, RE Marques, HR Carmo, A Borin, LD Coimbra, VO Boldrini, NS Brunetti, AS Vieira, E Mansour, RG Ulaf, AF Bernardes, TA Nunes, LC Ribeiro, AC Palma, MV Agrela, ML Moretti, AC Sposito, FB Pereira, LA Velloso, MAR Vinolo, A Damasio, JL Proença-Módena, RF Carvalho, MA Mori, D Martins-de-Souza, HI Nakaya, AS Farias and PM Moraes-Vieira
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.
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