Barberis Elettra, Vanella Virginia V, Falasca Marco, Caneapero Valeria, Cappellano Giuseppe, Raineri Davide, Ghirimoldi Marco, De Giorgis Veronica, Puricelli Chiara, Vaschetto Rosanna, Sainaghi Pier Paolo, Bruno Stefania, Sica Antonio, Dianzani Umberto, Rolla Roberta, Chiocchetti Annalisa, Cantaluppi Vincenzo, Baldanzi Gianluca, Marengo Emilio, Manfredi Marcello
Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy.
Center for Translational Research on Autoimmune and Allergic Diseases, University of Piemonte Orientale, Novara, Italy.
Front Mol Biosci. 2021 Feb 22;8:632290. doi: 10.3389/fmolb.2021.632290. eCollection 2021.
Knowledge of the host response to the novel coronavirus SARS-CoV-2 remains limited, hindering the understanding of COVID-19 pathogenesis and the development of therapeutic strategies. During the course of a viral infection, host cells release exosomes and other extracellular vesicles carrying viral and host components that can modulate the immune response. The present study used a shotgun proteomic approach to map the host circulating exosomes' response to SARS-CoV-2 infection. We investigated how SARS-CoV-2 infection modulates exosome content, exosomes' involvement in disease progression, and the potential use of plasma exosomes as biomarkers of disease severity. A proteomic analysis of patient-derived exosomes identified several molecules involved in the immune response, inflammation, and activation of the coagulation and complement pathways, which are the main mechanisms of COVID-19-associated tissue damage and multiple organ dysfunctions. In addition, several potential biomarkers-such as fibrinogen, fibronectin, complement C1r subcomponent and serum amyloid P-component-were shown to have a diagnostic feature presenting an area under the curve (AUC) of almost 1. Proteins correlating with disease severity were also detected. Moreover, for the first time, we identified the presence of SARS-CoV-2 RNA in the exosomal cargo, which suggests that the virus might use the endocytosis route to spread infection. Our findings indicate circulating exosomes' significant contribution to several processes-such as inflammation, coagulation, and immunomodulation-during SARS-CoV-2 infection. The study's data are available via ProteomeXchange with the identifier PXD021144.
目前对于宿主对新型冠状病毒SARS-CoV-2的反应的了解仍然有限，这阻碍了对COVID-19发病机制的理解以及治疗策略的开发。在病毒感染过程中，宿主细胞会释放携带病毒和宿主成分的外泌体及其他细胞外囊泡，这些成分可调节免疫反应。本研究采用鸟枪法蛋白质组学方法来描绘宿主循环外泌体对SARS-CoV-2感染的反应。我们研究了SARS-CoV-2感染如何调节外泌体内容物、外泌体在疾病进展中的作用，以及血浆外泌体作为疾病严重程度生物标志物的潜在用途。对患者来源的外泌体进行蛋白质组分析，确定了几种参与免疫反应、炎症以及凝血和补体途径激活的分子，这些是与COVID-19相关的组织损伤和多器官功能障碍的主要机制。此外，几种潜在的生物标志物，如纤维蛋白原、纤连蛋白、补体C1r亚成分和血清淀粉样蛋白P成分，显示出具有诊断特征，曲线下面积（AUC）几乎为1。还检测到了与疾病严重程度相关的蛋白质。此外，我们首次在外泌体货物中鉴定出SARS-CoV-2 RNA的存在，这表明病毒可能利用内吞途径传播感染。我们的研究结果表明，循环外泌体在SARS-CoV-2感染期间对炎症、凝血和免疫调节等多个过程有重大贡献。该研究的数据可通过ProteomeXchange获得，标识符为PXD021144。
