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

Autor: Carlos Alberto Oliveira de Biagi Junior, Natalia S Brunetti, Robson Francisco Carvalho, André Schwambach Vieira, Victor Corasolla Carregari, Ana Campos Codo, Eli Mansour, Maria Luiza Moretti, Raisa G. Ulaf, Lais D. Coimbra, Stéfanie Primon Muraro, Licio A. Velloso, Juliana Silveira Prodonoff, Thyago A. Nunes, Lauar de Brito Monteiro, Karina Bispo dos Santos, Alexandre Borin, Guilherme Reis-de-Oliveira, André Damasio, Andrei C. Sposito, Marcus V. Agrela, Gabriela Fabiano de Souza, Fernanda Crunfli, Daniel A. Toledo-Teixeira, Helder I. Nakaya, Gustavo Gastão Davanzo, Daniel Martins-de-Souza, Pierina Lorencini Parise, Pedro M. Moraes-Vieira, Jeffersson Leandro Jimenez Restrepo, Vinícius O. Boldrini, Rafael Elias Marques, Alessandro S. Farias, João Victor Virgilio-da-Silva, Andre C. Palma, A. F. Bernardes, Fabrício Bíscaro Pereira, Helison R. Carmo, Marcelo A. Mori, Luciana C. Ribeiro, José Luiz Proença-Módena, Pedro Henrique Vendramini, Marco Aurélio Ramirez Vinolo, M. C. Martini
Přispěvatelé: Universidade Estadual de Campinas (UNICAMP), Universidade de São Paulo (USP), Brazilian Biosciences National Laboratory (LNBio), Universidade Estadual Paulista (Unesp), D'Or Institute for Research and Education (IDOR), Conselho Nacional de Desenvolvimento Científico e Tecnológico
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Mitochondrial ROS
Blood Glucose
Male
Physiology
Mitochondrion
Monocytes
0302 clinical medicine
Medicine
diabetes
HIF-1alpha
Endocrine system and metabolic diseases
interferon
glycolysis
Middle Aged
Research Highlight
mitochondria
medicine.anatomical_structure
monocyte
Female
medicine.symptom
Signal transduction
Covid-19
Coronavirus Infections
Glycolysis
Signal Transduction
Adult
Pneumonia
Viral
Inflammation
Lung injury
Cell Line
Diabetes Complications
03 medical and health sciences
Betacoronavirus
Immune system
Diabetes Mellitus
Humans
Pandemics
Molecular Biology
business.industry
SARS-CoV-2
Monocyte
Correction
COVID-19
Cell Biology
medicine.disease
Hypoxia-Inducible Factor 1
alpha Subunit
030104 developmental biology
inflammation
Immunology
business
Cytokine storm
Reactive Oxygen Species
metabolism
030217 neurology & neurosurgery
Zdroj: Cell Metabolism
Signal Transduction and Targeted Therapy
Scopus
Repositório Institucional da UNESP
Universidade Estadual Paulista (UNESP)
instacron:UNESP
Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP
ISSN: 1550-4131
DOI: 10.1016/j.cmet.2020.07.007
Popis: 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
Databáze: OpenAIRE
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