文献类型: 外文期刊
作者: Cheng, Jinghua 1 ; Tao, Jie 1 ; Li, Benqiang 1 ; Shi, Ying 1 ; Liu, Huili 1 ;
作者机构: 1.Shanghai Acad Agr Sci, Inst Anim Sci & Vet Med, Shanghai 201106, Peoples R China
2.Shanghai Key Lab Agr Genet Breeding, Shanghai 201106, Peoples R China
3.Shanghai Engn Res Ctr Pig Breeding, Shanghai 201302, Peoples R China
关键词: Swine influenza virus; Proteomics analysis; Ferroptosis; Iron disorder
期刊名称:VIROLOGY JOURNAL ( 影响因子:5.913; 五年影响因子:4.372 )
ISSN:
年卷期: 2022 年 19 卷 1 期
页码:
收录情况: SCI
摘要: Background: Recently, Influenza A virus (IAV) has been shown to activate several programmed cell death pathways that play essential roles in host defense. Indeed, cell death caused by viral infection may be mediated by a mixed pattern of cell death instead of a certain single mode. Ferroptosis is a novel form of regulated cell death (RCD) that is mainly mediated by iron-dependent lipid peroxidation. Based on the proteomic data, we wondered whether IAV causes ferroptosis in host cells. Method: In this study, a quantitative proteomics approach based on an iTRAQ combined with LC-MS/MS was used to profile proteins expressed in A549 cells infected with H1N1 swine influenza virus (Sly). Meanwhile, we measured the intracellular iron content, reactive oxygen species (ROS) release and lipid peroxidation in response to SIV infection. Finally, a drug experiment was conducted to investigate the effects of ferroptosis on modulating SIV survival. Results: The bioinformatics analysis revealed several proteins closely relevant to iron homeostasis and transport, and the ferroptosis signaling pathway are highly enriched in response to SIV infection. In our experiment, aberrant expression of iron-binding proteins disrupted labile iron uptake and storage after SIV infection. Meanwhile, SIV infection inhibited system the Xc(-)/GPX4 axis resulting in GSH depletion and the accumulation of lipid peroxidation products. Notably, cell death caused by SIV as a result of iron-dependent lipid peroxidation can be partially rescued by ferroptosis inhibitor. Additionally, blockade of the ferroptotic pathway by ferrostatin-1 (Fer-1) treatment decreased viral titers and inflammatory response. Conclusions: This study revealed a new mode of cell death induced by IAV infection, and our findings might improve the understanding of the underlying mechanism involved in the interaction of virus and host cells.
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