Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis.
Cell Metab
; 32(3): 437-446.e5, 2020 09 01.
Article
en En
| MEDLINE
| ID: mdl-32697943
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-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-1É may have great therapeutic potential for the development of novel drugs to treat COVID-19.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
4_TD
Problema de salud:
4_pneumonia
Asunto principal:
Neumonía Viral
/
Glucemia
/
Monocitos
/
Infecciones por Coronavirus
/
Complicaciones de la Diabetes
/
Subunidad alfa del Factor 1 Inducible por Hipoxia
/
Betacoronavirus
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Cell Metab
Asunto de la revista:
METABOLISMO
Año:
2020
Tipo del documento:
Article
País de afiliación:
Brasil