SARS-CoV-2 Accessory Protein Orf7b Induces Lung Injury via c-Myc Mediated Apoptosis and Ferroptosis.
SARS-CoV-2 Accessory Protein Orf7b Induces Lung Injury via c-Myc Mediated Apoptosis and Ferroptosis.
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SARS-CoV-2辅助蛋白Orf 7 b通过c-Myc介导的细胞凋亡和铁凋亡诱导肺损伤
DOI：
10.3390/ijms25021157
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发表时间：
2024-01-18
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
2019年冠状病毒病大流行(新冠肺炎)已成为现代全球公共卫生面临的首要挑战。呼吸道是严重急性呼吸窘迫综合征冠状病毒2(SARS-CoV-2)感染的主要目标，大量细胞死亡和肺损伤是暴露的显著特征。导致细胞死亡和肺损伤的病毒因素仍然不完全清楚。因此，这项研究调查了开放阅读框架7b(Orf7b)，病毒的一种辅助蛋白，在导致肺损伤中的作用。在筛选病毒蛋白时，我们发现Orf7b是介导肺上皮细胞死亡的主要病毒因子之一。Orf7b的过表达导致肺上皮细胞的凋亡和铁下垂，而凋亡和铁下垂的抑制剂可阻断Orf7b诱导的细胞死亡。Orf7b上调转录调节因子c-Myc，c-Myc在肺细胞死亡途径的激活中是不可或缺的。耗尽c-Myc可减轻小鼠模型中的细胞凋亡和铁链细胞死亡以及肺损伤。我们的研究表明，Orf7b在新冠肺炎暴露所致的细胞死亡和肺损伤中发挥了重要作用，支持其作为潜在的治疗靶点。
The pandemic of coronavirus disease 2019 (COVID-19) has been the foremost modern global public health challenge. The airway is the primary target in severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) infection, with substantial cell death and lung injury being signature hallmarks of exposure. The viral factors that contribute to cell death and lung injury remain incompletely understood. Thus, this study investigated the role of open reading frame 7b (Orf7b), an accessory protein of the virus, in causing lung injury. In screening viral proteins, we identified Orf7b as one of the major viral factors that mediates lung epithelial cell death. Overexpression of Orf7b leads to apoptosis and ferroptosis in lung epithelial cells, and inhibitors of apoptosis and ferroptosis ablate Orf7b-induced cell death. Orf7b upregulates the transcription regulator, c-Myc, which is integral in the activation of lung cell death pathways. Depletion of c-Myc alleviates both apoptotic and ferroptotic cell deaths and lung injury in mouse models. Our study suggests a major role of Orf7b in the cell death and lung injury attributable to COVID-19 exposure, supporting it as a potential therapeutic target.
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影响因子：
7
作者：
Huang C;Santofimia-Castaño P;Liu X;Xia Y;Peng L;Gotorbe C;Neira JL;Tang D;Pouyssegur J;Iovanna J
通讯作者：
Iovanna J
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
EGLN1/c-Myc 诱导的淋巴特异性解旋酶通过脂质代谢基因表达变化抑制铁死亡
影响因子：
12.4
作者：
Jiang Y;Mao C;Yang R;Yan B;Shi Y;Liu X;Lai W;Liu Y;Wang X;Xiao D;Zhou H;Cheng Y;Yu F;Cao Y;Liu S;Yan Q;Tao Y
通讯作者：
Tao Y
影响因子：
22.7
作者：
Alborzinia, Hamed;Florez, Andres F.;Kreth, Sina;Brueckner, Lena M.;Yildiz, Umut;Gartlgruber, Moritz;Odoni, Dorett, I;Poschet, Gernot;Garbowicz, Karolina;Shao, Chunxuan;Klein, Corinna;Meier, Jasmin;Zeisberger, Petra;Nadler-Holly, Michal;Ziehm, Matthias;Paul, Franziska;Burhenne, Juergen;Bell, Emma;Shaikhkarami, Marjan;Wuerth, Roberto;Stainczyk, Sabine A.;Wecht, Elisa M.;Kreth, Jochen;Buettner, Michael;Ishaque, Naveed;Schlesner, Matthias;Nicke, Barbara;Stresemann, Carlo;Llamazares-Prada, Maria;Reiling, Jan H.;Fischer, Matthias;Amit, Ido;Selbach, Matthias;Herrmann, Carl;Woelfl, Stefan;Henrich, Kai-Oliver;Hoefer, Thomas;Trumpp, Andreas;Westermann, Frank
通讯作者：
Westermann, Frank
影响因子：
6.4
作者：
通讯作者：
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