新型冠状病毒的核衣壳蛋白和刺突蛋白驱动中性粒细胞胞外诱捕网的形成。

Nucleocapsid and Spike Proteins of SARS-CoV-2 Drive Neutrophil Extracellular Trap Formation.

作者信息

Youn Young-Jin, Lee Yu-Bin, Kim Sun-Hwa, Jin Hee Kyung, Bae Jae-Sung, Hong Chang-Won

机构信息

Department of Physiology, School of Medicine, Kyungpook National University, Daegu 41944, Korea.

Department of Laboratory Animal Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu 41944, Korea.

出版信息

Immune Netw. 2021 Feb 23;21(2):e16. doi: 10.4110/in.2021.21.e16. eCollection 2021 Apr.

Abstract

Patients with severe coronavirus disease 2019 (COVID-19) demonstrate dysregulated immune responses including exacerbated neutrophil functions. Massive neutrophil infiltrations accompanying neutrophil extracellular trap (NET) formations are also observed in patients with severe COVID-19. However, the mechanism underlying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced NET formation has not yet been elucidated. Here we show that 2 viral proteins encoded by SARS-CoV-2, the nucleocapsid protein and the whole spike protein, induce NET formation from neutrophils. NET formation was ROS-independent and was completely inhibited by the spleen tyrosine kinase inhibition. The inhibition of p38 MAPK, protein kinase C, and JNK signaling pathways also inhibited viral protein-induced NET formation. Our findings demonstrate one method by which SARS-CoV-2 evades innate immunity and provide a potential target for therapeutics to treat patients with severe COVID-19.

摘要

患有严重2019冠状病毒病(COVID-19)的患者表现出免疫反应失调,包括中性粒细胞功能加剧。在重症COVID-19患者中也观察到伴随着中性粒细胞胞外陷阱(NET)形成的大量中性粒细胞浸润。然而,严重急性呼吸综合征冠状病毒2(SARS-CoV-2)诱导NET形成的机制尚未阐明。在此我们表明,SARS-CoV-2编码的两种病毒蛋白,核衣壳蛋白和完整的刺突蛋白,可诱导中性粒细胞形成NET。NET形成不依赖于活性氧(ROS),并被脾酪氨酸激酶抑制完全阻断。对p38丝裂原活化蛋白激酶(MAPK)、蛋白激酶C和c-Jun氨基末端激酶(JNK)信号通路的抑制也抑制了病毒蛋白诱导的NET形成。我们的研究结果证明了SARS-CoV-2逃避先天免疫的一种方式,并为治疗重症COVID-19患者提供了潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84b8/8099611/7186064e88b3/in-21-e16-g001.jpg

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