Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis
Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis
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DOI：
10.1016/j.cmet.2020.07.007
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发表时间：
2020-09-01
期刊：
影响因子：
29
通讯作者：
Moraes-Vieira, Pedro M.
中科院分区：
文献类型：
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作者：
Codo, Ana Campos;Davanzo, Gustavo Gastao;Moraes-Vieira, Pedro M.
COVID-19可导致严重的肺损伤。为什么血糖水平不受控制的糖尿病患者更容易患上严重的COVID-19，这一点仍有待确定。SARS-CoV-2感染的分子机制以及在严重COVID-19患者中发现的细胞因子风暴的发生原因尚不清楚。单核细胞和巨噬细胞是COVID-19患者肺部最丰富的免疫细胞类型，似乎在疾病的致病性中发挥核心作用。这些细胞在感染后适应它们的代谢，并变得高度糖酵解，这有助于SARS-CoV-2的复制。感染触发线粒体ROS产生，其诱导低氧诱导因子-1 α（HIF-1 α）的稳定，从而促进糖酵解。SARSCoV-2感染引起的HIF-1 α诱导的单核细胞代谢变化直接抑制T细胞应答并降低上皮细胞存活。靶向HIF-1 α可能对开发治疗COVID-19的新药具有巨大的治疗潜力。
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.