Author(s):
Codo, Ana Campos ; 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.
Date: 2020
Persistent ID: http://hdl.handle.net/11449/201151
Origin: Oasisbr
Subject(s): Covid-19; diabetes; glycolysis; HIF-1alpha; inflammation; interferon; metabolism; mitochondria; monocyte; SARS-CoV-2
Description
Made available in DSpace on 2020-12-12T02:25:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-09-01
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Fundo de Apoio ao Ensino, à Pesquisa e Extensão, Universidade Estadual de Campinas
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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.
Laboratory of Immunometabolism Department of Genetics Evolution Microbiology and Immunology Institute of Biology University of Campinas
Department of Genetics Evolution Microbiology and Immunology Institute of Biology University of Campinas
Department of Biochemistry and Tissue Biology Institute of Biology University of Campinas
Department of Genetics at Ribeirao Preto Medical School University of Sao Paulo, Ribeirao Preto
Department of Clinical and Toxicological analyses School of Pharmaceutical Sciences University of São Paulo
Brazilian Biosciences National Laboratory (LNBio), Campinas
Department of Animal Biology Institute of Biology University of Campinas, Campinas
Department of Internal Medicine School of Medical Sciences University of Campinas, Campinas
Department of Clinical Medicine School of Medical Sciences University of Campinas, Campinas
Hematology and Hemotherapy Center University of Campinas, Campinas
Obesity and Comorbidities Research Center (OCRC) University of Campinas
Experimental Medicine Research Cluster (EMRC) University of Campinas
Department of Structural and Functional Biology Institute of Biosciences São Paulo State University (UNESP), Botucatu
D'Or Institute for Research and Education (IDOR)
Instituto Nacional de Biomarcadores em Neuropsiquiatria Conselho Nacional de Desenvolvimento Científico e Tecnológico
Department of Structural and Functional Biology Institute of Biosciences São Paulo State University (UNESP), Botucatu
FAPESP: 20/04579-7
FAPESP: 2015/15626-8
FAPESP: 2016/18031-8
FAPESP: 2016/23328-0
FAPESP: 2017/01184-9
FAPESP: 2018/22505-0
FAPESP: 2019/00098-7
FAPESP: 2019/06372-3
FAPESP: 2020/04522-5
FAPESP: 2020/04558-0
FAPESP: 2020/04583-4
FAPESP: 2020/04746-0
FAPESP: 2020/04919-2
Fundo de Apoio ao Ensino, à Pesquisa e Extensão, Universidade Estadual de Campinas: 2274/20
