Department of Medical Laboratory Sciences, Collage of Health Sciences, University of Sharjah, Sharjah, UAE.
Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, UAE.
PLoS One. 2023 Jan 19;18(1):e0280592. doi: 10.1371/journal.pone.0280592. eCollection 2023.
The large-scale dissemination of coronavirus disease-2019 (COVID-19) and its serious complications have pledged the scientific research communities to uncover the pathogenesis mechanisms of its etiologic agent, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Methods of unveiling such mechanisms are rooted in understanding the viral agent's interactions with the immune system, including its ability to activate macrophages, due to their suggested role in prolonged inflammatory phases and adverse immune responses. The objective of this study is to test the effect of SARS-CoV-2-free proteins on the metabolic and immune responses of macrophages. We hypothesized that SARS-CoV-2 proteins shed during the infection cycle may dynamically induce metabolic and immunologic alterations with an inflammatory impact on the infected host cells. It is imperative to delineate such alterations in the context of macrophages to gain insight into the pathogenesis of these highly infectious viruses and their associated complications and thus, expedite the vaccine and drug therapy advent in combat of viral infections. Human monocyte-derived macrophages were treated with SARS-CoV-2-free proteins at different concentrations. The phenotypic and metabolic alterations in macrophages were investigated and the subsequent metabolic pathways were analyzed. The obtained results indicated that SARS-CoV-2-free proteins induced concentration-dependent alterations in the metabolic and phenotypic profiles of macrophages. Several metabolic pathways were enriched following treatment, including vitamin K, propanoate, and the Warburg effect. These results indicate significant adverse effects driven by residual viral proteins that may hence be considered determinants of viral pathogenesis. These findings provide important insight as to the impact of SARS-CoV-2-free residual proteins on the host cells and suggest a potential new method of management during the infection and prior to vaccination.
大规模传播的 2019 年冠状病毒病（COVID-19）及其严重并发症促使科学界深入研究其病原体，即严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的发病机制。揭示这些机制的方法源于理解病毒与免疫系统的相互作用，包括其激活巨噬细胞的能力，因为它们被认为在炎症持续期和不良免疫反应中发挥作用。本研究旨在测试 SARS-CoV-2 无蛋白对巨噬细胞代谢和免疫反应的影响。我们假设感染周期中脱落的 SARS-CoV-2 蛋白可能会动态诱导代谢和免疫改变，对感染宿主细胞产生炎症影响。在巨噬细胞的背景下阐明这些改变对于深入了解这些高传染性病毒及其相关并发症的发病机制至关重要，从而加速疫苗和药物治疗在对抗病毒感染中的应用。用不同浓度的 SARS-CoV-2 无蛋白处理人单核细胞衍生的巨噬细胞。研究了巨噬细胞的表型和代谢改变，并分析了随后的代谢途径。结果表明，SARS-CoV-2 无蛋白诱导巨噬细胞的代谢和表型特征呈浓度依赖性改变。处理后有几个代谢途径被富集，包括维生素 K、丙酸盐和瓦博格效应。这些结果表明，残留的病毒蛋白可能会产生显著的不良反应，因此可以被认为是病毒发病机制的决定因素。这些发现为 SARS-CoV-2 无残留蛋白对宿主细胞的影响提供了重要的见解，并为感染和接种疫苗前的管理提供了一种潜在的新方法。
