生物
细胞生物学
相互作用体
免疫系统
跨膜蛋白
干扰素
跨膜结构域
信号转导
冠状病毒
病毒学
免疫学
氨基酸
基因
生物化学
2019年冠状病毒病(COVID-19)
传染病(医学专业)
受体
病理
疾病
医学
作者
Ana Dominguez Andres,Yongmei Feng,Alexandre Rosa Campos,Jun Yin,Changjun Yang,Brian P. James,Rabi Murad,Hyungsoo Kim,Aniruddha J. Deshpande,David E. Gordon,Nevan J. Krogan,Raffaella Pippa
标识
DOI:10.1101/2020.08.18.256776
摘要
Abstract Disrupted antiviral immune responses are associated with severe COVID-19, the disease caused by SAR-CoV-2. Here, we show that the 73-amino-acid protein encoded by ORF9c of the viral genome contains a putative transmembrane domain, interacts with membrane proteins in multiple cellular compartments, and impairs antiviral processes in a lung epithelial cell line. Proteomic, interactome, and transcriptomic analyses, combined with bioinformatic analysis, revealed that expression of only this highly unstable small viral protein impaired interferon signaling, antigen presentation, and complement signaling, while inducing IL-6 signaling. Furthermore, we showed that interfering with ORF9c degradation by either proteasome inhibition or inhibition of the ATPase VCP blunted the effects of ORF9c. Our study indicated that ORF9c enables immune evasion and coordinates cellular changes essential for the SARS-CoV-2 life cycle. One-sentence summary SARS-CoV-2 ORF9c is the first human coronavirus protein localized to membrane, suppressing antiviral response, resembling full viral infection.
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