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单核细胞糖酵解升高促进新冠病毒感染
作者:小柯机器人 发布时间:2020/7/21 8:45:48

巴西坎皮纳斯大学Pedro Manoel M. Moraes-Vieira研究小组发现,单核细胞糖酵解升高促进新冠病毒(SARS-CoV-2)感染。该项研究成果于2020年7月17日在线发表在《细胞—代谢》杂志上。

研究人员表示,COVID-19可导致严重的肺损伤。尚需确定为什么血糖水平不受控制的糖尿病患者更容易发展出严重的COVID-19。SARS-CoV-2感染的分子机制以及决定严重COVID-19患者中细胞因子风暴的起因还不清楚。单核细胞/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起着核心作用。
 
研究人员发现,这些细胞在感染后适应其新陈代谢并变得高度糖酵解,从而促进SARS-CoV-2复制。感染会触发线粒体ROS的产生,从而诱导缺氧诱导因子1α(HIF-1α)的稳定,进而促进糖酵解。HIF-1α引起的单核细胞代谢变化直接抑制T细胞反应并降低上皮细胞存活率。靶向HIF-1ɑ对于开发治疗COVID-19的新药物可能具有巨大潜力。
 
附:英文原文

Title: Elevated glucose levels favor SARS-CoV-2 infection and monocyte response through a HIF-1α/glycolysis dependent axis

Author: Ana Campos Codo, Gustavo Gasto Davanzo, Lauar de Brito Monteiro, Gabriela Fabiano de Souza, Stéfanie Primon Muraro, Joo Victor Virgilio-da-Silva, Juliana Silveira Prodonoff, Victor Corasolla Carregari, Carlos Alberto Oliveira de Biagi Junior, Fernanda Crunfli, Jeffersson Leandro Jimenez Restrepo, Pedro Henrique Vendramini, Guilherme Reis-de-Oliveira, Karina Bispo dos Santos, Daniel Augusto de Toledo Teixeira, Pierina Lorencini Parise, Matheus Cavalheiro Martini, Rafael Elias Marques, Helison R. Carmo, Alexandre Borin, Laís Duro Coimbra, Vinícius O. Boldrini, Natalia S. Brunetti, Andre S. Vieira, Eli Mansour, Raisa G. Ulaf, Ana F. Bernardes, Thyago A. Nunes, Luciana C. Ribeiro, Andre C. Palma, Marcus V. Agrela, Maria Luiza Moretti, Andrei C. Sposito, Fabrício Bíscaro Pereira, Licio Augusto Velloso, Marco Aurélio Ramirez Vinolo, André Damasio, José Luiz Proena-Módena, Robson Francisco Carvalho, Marcelo A. Mori, Daniel Martins-de-Souza, Helder I. Nakaya, Alessandro S. Farias, Pedro Manoel M. Moraes-Vieira

Issue&Volume: 2020-07-17

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/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.

DOI: 10.1016/j.cmet.2020.07.007

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30365-X

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:22.415
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx