Virus-Host Interactome and Proteomic Survey Reveal Potential Virulence Factors Influencing SARS-CoV-2 Pathogenesis
Virus-Host Interactome and Proteomic Survey Reveal Potential Virulence Factors Influencing SARS-CoV-2 Pathogenesis
复制标题
病毒-宿主相互作用组和蛋白质组学调查揭示了影响 SARS-CoV-2 发病机制的潜在毒力因素
DOI：
10.1016/j.medj.2020.07.002
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发表时间：
2021-01-15
期刊：
影响因子：
17
通讯作者：
Liang, Qiming
中科院分区：
文献类型：
--
作者：
Li, Jingjiao;Guo, Mingquan;Liang, Qiming
背景资料：由严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）引起的2019年冠状病毒病（COVID-19）大流行正在持续，由于相对容易在人与人之间传播，目前缺乏有效的抗病毒治疗，因此是全球公共卫生问题。然而，SARS-CoV-2致病的确切分子机制在很大程度上仍然未知。方法：全基因组筛选用于建立病毒内和病毒宿主相互作用组。本研究采用定量蛋白质组学方法对COVID-19患者外周血单个核细胞（PBMC）蛋白质组特征进行了研究。严重COVID-19 PBMC中的这一特征揭示了与中性粒细胞活化和血液凝固相关的细胞蛋白的显著上调，以及介导T细胞受体信号传导的蛋白的下调。从相互作用组中，我们进一步确定了非结构蛋白10与NF-κ B抑制因子（NKRF）相互作用以促进白细胞介素-8（IL-8）诱导，这可能有助于IL-8介导的中性粒细胞趋化性和在COVID-19患者中观察到的过度兴奋的宿主炎症反应。我们的研究不仅系统地研究了SARS-CoV-2诱导的宿主靶点和细胞网络的扰动，而且还揭示了SARS-CoV-2触发细胞因子风暴的机制，代表了寻求治疗干预的强大资源。
Background: The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a global public health concern due to relatively easy person-to-person transmission and the current lack of effective antiviral therapy. However, the exact molecular mechanisms of SARS-CoV-2 pathogenesis remain largely unknown.Methods: Genome-wide screening was used to establish intraviral and viral-host interactomes. Quantitative proteomics was used to investigate the peripheral blood mononuclear cell (PBMC) proteome signature in COVID-19.Findings: We elucidated 286 host proteins targeted by SARS-CoV-2 and >350 host proteins that are significantly perturbed in COVID-19-derived PBMCs. This signature in severe COVID-19 PBMCs reveals a significant upregulation of cellular proteins related to neutrophil activation and blood coagulation, as well as a downregulation of proteins mediating T cell receptor signaling. From the interactome, we further identified that non-structural protein 10 interacts with NF-KB-repressing factor (NKRF) to facilitate interleukin-8 (IL-8) induction, which potentially contributes to IL-8-mediated chemotaxis of neutrophils and the overexuberant host inflammatory response observed in COVID-19 patients.Conclusions: Our study not only presents a systematic examination of SARS-CoV-2-induced perturbation of host targets and cellular networks but it also reveals insights into the mechanisms by which SARS-CoV-2 triggers cytokine storms, representing a powerful resource in the pursuit of therapeutic interventions.