Department of Virology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran.
Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
Microb Pathog. 2023 Oct;183:106300. doi: 10.1016/j.micpath.2023.106300. Epub 2023 Aug 9.
Tryptophanyl-tRNA synthetase (WRS) is a critical enzyme involved in protein synthesis, responsible for charging tRNA with the essential amino acid tryptophan. Recent studies have highlighted its novel role in stimulating innate immunity against bacterial and viral infections. However, the significance of WRS in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains elusive. In this study, we aimed to investigate the complex interplay between WRS, inflammatory markers, Toll-like receptor-4 (TLR-4), and clinical outcomes in coronavirus disease 19 (COVID-19) patients. A case-control investigation comprised 127 COVID-19 patients, carefully classified as severe or moderate upon admission, and 112 healthy individuals as a comparative group. Blood samples were meticulously collected before treatment initiation, and WRS, interleukin-6 (IL-6), and C-reactive protein (CRP) concentrations were quantified using a well-established commercial ELISA kit. Peripheral blood mononuclear cells (PBMCs) were isolated from the blood samples, and RNA was extracted for cDNA synthesis. Semi-quantitative real-time polymerase chain reaction (PCR) was employed to assess the relative expression of TLR-4. COVID-19 patients exhibited elevated levels of WRS, IL-6, CRP, and TLR-4 expression compared to healthy individuals, with the severe group displaying significantly higher levels than the moderate group. Notably, severe patients demonstrated substantial fluctuations in CRP, IL-6, and WRS levels over time, a pattern not observed in their moderate counterparts. Although no significant distinctions were observed in the dynamic alterations of WRS, IL-6, CRP, and TLR-4 expression between deceased and surviving patients, a trend emerged indicating higher IL-6_1 levels in deceased patients and elevated lactate dehydrogenase (LDH) levels in severe patients who succumbed to the disease. This pioneering research highlights the dynamic alterations of WRS in COVID-19 patients, providing valuable insights into the correlation between WRS, inflammatory markers, and disease severity within this population. Understanding the role of WRS in SARS-CoV-2 infection may open new avenues for therapeutic interventions targeting innate immunity to combat COVID-19.
色氨酰-tRNA 合成酶（WRS）是一种参与蛋白质合成的关键酶，负责将必需氨基酸色氨酸加载到 tRNA 上。最近的研究强调了它在刺激针对细菌和病毒感染的固有免疫中的新作用。然而，WRS 在严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染中的意义仍然难以捉摸。在这项研究中，我们旨在研究 WRS、炎症标志物、Toll 样受体 4（TLR-4）与 2019 年冠状病毒病（COVID-19）患者临床结局之间的复杂相互作用。一项病例对照研究包括 127 名 COVID-19 患者，根据入院时的严重程度或中度程度进行精心分类，112 名健康个体作为对照组。在开始治疗前采集血液样本，使用成熟的商业 ELISA 试剂盒定量测定 WRS、白细胞介素-6（IL-6）和 C 反应蛋白（CRP）浓度。从血液样本中分离外周血单核细胞（PBMCs），并提取 RNA 用于 cDNA 合成。采用半定量实时聚合酶链反应（PCR）评估 TLR-4 的相对表达。与健康个体相比，COVID-19 患者的 WRS、IL-6、CRP 和 TLR-4 表达水平升高，重度组的表达水平明显高于中度组。值得注意的是，严重组患者的 CRP、IL-6 和 WRS 水平随时间发生显著波动，而中度组患者则没有观察到这种模式。虽然在死亡和存活患者之间，WRS、IL-6、CRP 和 TLR-4 表达的动态变化没有观察到显著差异，但在死亡患者中观察到 IL-6_1 水平升高，在因疾病死亡的严重患者中观察到乳酸脱氢酶（LDH）水平升高的趋势。这项开创性的研究强调了 COVID-19 患者中 WRS 的动态变化，为 WRS、炎症标志物与该人群疾病严重程度之间的相关性提供了有价值的见解。了解 WRS 在 SARS-CoV-2 感染中的作用可能为针对固有免疫的治疗干预提供新途径，以对抗 COVID-19。
