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

Authors :
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
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
Source :
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
Publication Year :
2020
Publisher :
Elsevier BV, 2020.

Abstract

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

Details

Language :
English
ISSN :
15504131
Database :
OpenAIRE
Journal :
Cell Metabolism
Accession number :
edsair.doi.dedup.....2143060a61e4753e054c25c25cc99d65
Full Text :
https://doi.org/10.1016/j.cmet.2020.07.007