Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis

• Autor(a) principal: Codo, Ana Campos
• Data de Publicação: 2020
• Outros Autores: Davanzo, Gustavo Gastão, Monteiro, Lauar de Brito, de Souza, Gabriela Fabiano, Muraro, Stéfanie Primon, Virgilio-da-Silva, João Victor, Prodonoff, Juliana Silveira, Carregari, Victor Corasolla, de Biagi Junior, Carlos Alberto Oliveira, Crunfli, Fernanda, Jimenez Restrepo, Jeffersson Leandro, Vendramini, Pedro Henrique, Reis-de-Oliveira, Guilherme, Bispo dos Santos, Karina, Toledo-Teixeira, Daniel A., Parise, Pierina Lorencini, Martini, Matheus Cavalheiro, Marques, Rafael Elias, Carmo, Helison R., Borin, Alexandre, Coimbra, Laís Durço, Boldrini, Vinícius O., Brunetti, Natalia S., Vieira, Andre S., Mansour, Eli, Ulaf, Raisa G., Bernardes, Ana F., Nunes, Thyago A., Ribeiro, Luciana C., Palma, Andre C., Agrela, Marcus V., Moretti, Maria Luiza, Sposito, Andrei C., Pereira, Fabrício Bíscaro, Velloso, Licio Augusto, Vinolo, Marco Aurélio Ramirez, Damasio, André, Proença-Módena, José Luiz, Carvalho, Robson Francisco [UNESP], Mori, Marcelo A., Martins-de-Souza, Daniel, Nakaya, Helder I., Farias, Alessandro S., Moraes-Vieira, Pedro M.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1016/j.cmet.2020.07.007; http://hdl.handle.net/11449/201151
• topic: Covid-19; diabetes; glycolysis; HIF-1alpha; inflammation; interferon; metabolism; mitochondria; monocyte; SARS-CoV-2

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. Diabetic people with uncontrolled blood glucose levels have a greater risk to develop severe COVID-19 disease. Codo et al. show that elevated glucose levels and glycolysis promote SARS-CoV-2 (CoV-2) replication and cytokine production in monocytes through a mitochondrial ROS/hypoxia-inducible factor-1α dependent pathway, resulting in T cell dysfunction and epithelial cell death.