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Influenza A virus-induced glycolysis facilitates virus replication by activating ROS/HIF-1α pathway

文献类型： 外文期刊

作者： Zhang, Yijia 1 ; Chang, Lifeng 1 ; Xin, Xin 1 ; Qiao, Yixuan 1 ; Qiao, Wenna 1 ; Ping, Jihui 1 ; Xia, Jun 2 ; Su, Juan 1 ;

作者机构： 1.Nanjing Agr Univ, Coll Vet Med, Nanjing 210095, Peoples R China

2.Minist Agr & Rural Affairs, Inst Vet Med, Xinjiang Acad Anim Sci, Key Lab Prevent & Control Herbivorous Anim Dis, Xinjiang 830000, Peoples R China

3.Xinjiang Anim Dis Res Key Lab, Xinjiang 830000, Peoples R China

关键词： Influenza A virus; Mitochondria; ROS; HIF-1 alpha; Glycolysis; Lung

期刊名称：FREE RADICAL BIOLOGY AND MEDICINE （ 影响因子：8.2； 五年影响因子：8.6 ）

ISSN： 0891-5849

年卷期： 2024 年 225 卷

页码：

收录情况： SCI

摘要： As a highly contagious acute respiratory disease, influenza A virus (A/WSN/1933) poses a huge threat to human health and public health. influenza A virus proliferation relies on glucose metabolism in host cells, yet the effects of influenza A virus on glucose metabolism and the underlying molecular mechanisms remain unclear. Here, we created models of WSN virus-infected mice and A549 cells, along with analyzing metabolomics and transcriptomics data, to investigate how WSN virus infection affects host cell glucose metabolism and specific mechanisms. Analysis of metabolites and gene expression showed that WSN virus infection triggers glycolysis in A549 cells, with notable upregulation of hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), hypoxiainducible factor-1 alpha (HIF-1 alpha), and elevated lactate levels. Additionally, it leads to mitochondrial impairment and heightened reactive oxygen species (ROS) generation. Elevated levels of glucose may enhance the replication of WSN virus, whereas inhibitors of glycolysis can reduce it. Enhancement of HIF-1 alpha activation facilitated replication of WSN virus through stimulation of lactate synthesis, with the primary influence of glycolysis on WSN virus replication being mediated by ROS/HIF-1 alpha signaling. Mice given HIF-1 alpha inhibitor PTX478 or glycolysis inhibitor 2-Deoxyglucose (2-DG) exhibited reduced lactate levels and decreased WSN virus replication, along with mitigated weight loss and lung damage. In summary, WSN virus-induced glycolysis has been demonstrated to enhance virus replication through the activation of the ROS/HIF-1 alpha pathway, suggesting potential new targets for combating the virus.

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