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

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Codo, Ana Campos ; Davanzo, Gustavo Gastao ; Monteiro, Lauar de Brito ; de Souza, Gabriela Fabiano ; Muraro, Stefanie Primon ; Virgilio-da-Silva, Joao Victor ; Prodonoff, Juliana Silveira ; Carregari, Victor Corasolla ; Oliveira de Biagi Junior, Carlos Alberto ; Crunfli, Fernanda ; Jimenez Restrepo, Jeffersson Leandro ; Vendramini, Pedro Henrique ; Reis-de-Oliveira, Guilherme ; dos Santos, Karina Bispo ; Toledo-Teixeira, Daniel A. ; Parise, Pierina Lorencini ; Martini, Matheus Cavalheiro ; Marques, Rafael Elias ; Carmo, Helison R. ; Borin, Alexandre ; Coimbra, Lais Durco ; Boldrini, Vinicius 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, Fabricio Biscaro ; Velloso, Licio Augusto ; Ramirez Vinolo, Marco Aurelio ; Damasio, Andre ; Proenca-Modena, Jose Luiz ; Carvalho, Robson Francisco ; Mori, Marcelo A. ; Martins-de-Souza, Daniel ; Nakaya, Helder, I ; Farias, Alessandro S. ; Moraes-Vieira, Pedro M.

• Document type: Journal article
• Source: Cell Metabolism; v. 32, n. 3, p. 15-pg., 2020-09-01.

Abstract

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-1 alpha (HIF-1 alpha) and consequently promotes glycolysis. HIF-1 alpha-induced changes in monocyte metabolism by SARSCoV-2 infection directly inhibit T cell response and reduce epithelial cell survival. Targeting HIF-1 alpha may have great therapeutic potential for the development of novel drugs to treat COVID-19. (AU)

• FAPESP's process: 19/00098-7 - Multi-User Equipment approved in grant 2017/25588-1: cromatógrafo Acquity UPLC I-Class
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 20/04558-0 - Characterization of intrinsic risk factors and the development of new diagnostic and treatment alternatives for COVID-19
• Grantee: José Luiz Proença Módena
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/04522-5 - Clinical trial for bradykinin inhibition in hospitalized adults with COVID-19 grave
• Grantee: Licio Augusto Velloso
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/06372-3 - Multiparametric flow cytometry
• Grantee: Alessandro dos Santos Farias
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 16/18031-8 - HIF-1 alpha in metabolic and functional control of adipose tissue resident macrophages in diabetes induced by obesity
• Grantee: Gustavo Gastão Davanzo
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/15626-8 - Macrophages and T lymphocytes immunometabolism in metabolic and inflammatory diseases
• Grantee: Pedro Manoel Mendes de Moraes Vieira
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 16/23328-0 - Study of the metabolic regulation of macrophages by leptin
• Grantee: Lauar de Brito Monteiro
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 17/01184-9 - CAMeLEOm: cross-species analysis of metabolic, lifespan effects and omics of dietary restriction mimetics
• Grantee: Marcelo Alves da Silva Mori
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/04919-2 - Determining molecular candidates that contribute to the higher risk of COVID-19 in aged individuals
• Grantee: Marcelo Alves da Silva Mori
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/04583-4 - Impact of intestinal microbiota and its metabolites on SARS-CoV-2 infection
• Grantee: Marco Aurélio Ramirez Vinolo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/04579-7 - Study of the risk factors associated with greater severity to COVID-19 and mapping of the metabolic pathways required for the anti-SARS-CoV-2 response
• Grantee: Pedro Manoel Mendes de Moraes Vieira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/22505-0 - Effect of 12-oleic acid ester of hydroxy fatty acid (12-OAHSA) on inflammatory and metabolic pathways of macrophage activation
• Grantee: Ana Campos Codo
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 20/04746-0 - Understanding the molecular bases and the role of risk factors associated to SARS-CoV-2 infection in preclinical models
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Regular Research Grants