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

被引：672

作者：

Codo, Ana Campos ^{[1
]}

Davanzo, Gustavo Gastao ^{[1
]}

Monteiro, Lauar de Brito ^{[1
]}

de Souza, Gabriela Fabiano ^{[2
]}

Muraro, Stefanie Primon ^{[2
]}

Virgilio-da-Silva, Joao Victor ^{[1
]}

Prodonoff, Juliana Silveira ^{[1
]}

Carregari, Victor Corasolla ^{[3
]}

Oliveira de Biagi Junior, Carlos Alberto ^{[4
]}

Crunfli, Fernanda ^{[3
]}

Jimenez Restrepo, Jeffersson Leandro ^{[5
]}

Vendramini, Pedro Henrique ^{[3
]}

Reis-de-Oliveira, Guilherme ^{[3
]}

dos Santos, Karina Bispo ^{[2
]}

Toledo-Teixeira, Daniel A. ^{[2
]}

Parise, Pierina Lorencini ^{[2
]}

Martini, Matheus Cavalheiro ^{[2
]}

Marques, Rafael Elias ^{[6
]}

Carmo, Helison R. ^{[9
]}

Borin, Alexandre ^{[6
]}

Coimbra, Lais Durco ^{[6
]}

Boldrini, Vinicius O. ^{[2
]}

Brunetti, Natalia S. ^{[2
]}

Vieira, Andre S. ^{[7
]}

Mansour, Eli ^{[8
]}

Ulaf, Raisa G. ^{[8
]}

Bernardes, Ana F. ^{[8
]}

Nunes, Thyago A. ^{[8
]}

Ribeiro, Luciana C. ^{[8
]}

Palma, Andre C. ^{[8
]}

Agrela, Marcus, V ^{[8
]}

Moretti, Maria Luiza ^{[8
]}

Sposito, Andrei C. ^{[9
]}

Pereira, Fabricio Biscaro ^{[10
]}

Velloso, Licio Augusto ^{[8
,11
]}

Ramirez Vinolo, Marco Aurelio ^{[2
,12
]}

Damasio, Andre ^{[3
,12
]}

Proenca-Modena, Jose Luiz ^{[2
]}

Carvalho, Robson Francisco ^{[13
]}

Mori, Marcelo A. ^{[3
,11
,12
]}

Martins-de-Souza, Daniel ^{[3
,12
,14
,15
]}

Nakaya, Helder, I ^{[5
]}

Farias, Alessandro S. ^{[2
,12
]}

Moraes-Vieira, Pedro M. ^{[1
,11
,12
]}

机构：

[1] Univ Estadual Campinas, Lab Immunometab, Dept Genet Evolut Microbiol & Immunol, Inst Biol, Campinas, SP, Brazil

[2] Univ Estadual Campinas, Inst Biol, Dept Genet Evolut Microbiol & Immunol, Campinas, SP, Brazil

[3] Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, Campinas, SP, Brazil

[4] Univ Sao Paulo, Dept Genet, Ribeirao Preto Med Sch, Ribeirao Preto, SP, Brazil

[5] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo, Brazil

[6] Brazilian Biosci Natl Lab LNBio, Campinas, SP, Brazil

[7] Univ Estadual Campinas, Inst Biol, Dept Anim Biol, Campinas, SP, Brazil

[8] Univ Estadual Campinas, Sch Med Sci, Dept Internal Med, Campinas, SP, Brazil

[9] Univ Estadual Campinas, Sch Med Sci, Dept Clin Med, Campinas, SP, Brazil

[10] Univ Estadual Campinas, Hematol & Hemotherapy Ctr, Campinas, SP, Brazil

[11] Univ Estadual Campinas, Obes & Comorbid Res Ctr OCRC, Sao Paulo, Brazil

[12] Univ Estadual Campinas, Expt Med Res Cluster EMRC, Sao Paulo, Brazil

[13] Sao Paulo State Univ UNESP, Inst Biosci, Dept Struct & Funct Biol, Botucatu, SP, Brazil

[14] DOr Inst Res & Educ IDOR, Sao Paulo, Brazil

[15] Conselho Nacl Desenvolvimento Cient & Tecnol, Inst Nacl Biomarcadores Neuropsiquiatria, Sao Paulo, Brazil

来源：

CELL METABOLISM | 2020年 / 32卷 / 03期

基金：

巴西圣保罗研究基金会;

关键词：

SUCCINATE;

D O I：

10.1016/j.cmet.2020.07.007

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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.

引用

页码：437 / +

页数：15

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