Khalid Zunera, Huan Ma, Sohail Raza Muhammad, Abbas Misbah, Naz Zara, Kombe Kombe Arnaud John, Zeng Weihong, He Hongliang, Jin Tengchuan
Division of Life Sciences and Medicine, Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China (USTC), University of Science and Technology of China, Hefei, China.
CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
Front Microbiol. 2022 Aug 2;13:901848. doi: 10.3389/fmicb.2022.901848. eCollection 2022.
Due to fast transmission and various circulating SARS-CoV-2 variants, a significant increase of coronavirus 2019 infection cases with acute respiratory symptoms has prompted worries about the efficiency of current vaccines. The possible evasion from vaccine immunity urged scientists to identify novel therapeutic targets for developing improved vaccines to manage worldwide COVID-19 infections. Our study sequenced pooled peripheral blood mononuclear cells transcriptomes of SARS-CoV-2 patients with moderate and critical clinical outcomes to identify novel potential host receptors and biomarkers that can assist in developing new translational nanomedicines and vaccine therapies. The dysregulated signatures were associated with humoral immune responses in moderate and critical patients, including B-cell activation, cell cycle perturbations, plasmablast antibody processing, adaptive immune responses, cytokinesis, and interleukin signaling pathway. The comparative and longitudinal analysis of moderate and critically infected groups elucidated diversity in regulatory pathways and biological processes. Several immunoglobin genes , and , ribosomal proteins , and , inflammatory response related cytokines including Tumor Necrosis Factor , and , C-C motif chemokine ligands , and , C-X-C motif chemokine ligands , and and genes related to cell cycle process and DNA proliferation (, and ) were significantly upregulated among SARS-CoV-2 infected patients. 60S Ribosomal protein L29 was a highly expressed gene among all COVID-19 infected groups. Our study suggested that identifying differentially expressed genes (DEGs) based on disease severity and onset can be a powerful approach for identifying potential therapeutic targets to develop effective drug delivery systems against SARS-CoV-2 infections. As a result, potential therapeutic targets, such as the RPL29 protein, can be tested and to develop future mRNA-based translational nanomedicines and therapies to combat SARS-CoV-2 infections.
由于传播速度快以及严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）的各种循环变体，2019冠状病毒感染伴有急性呼吸道症状的病例显著增加，引发了人们对当前疫苗效力的担忧。疫苗免疫可能出现的逃逸促使科学家们寻找新的治疗靶点，以开发更好的疫苗来应对全球范围内的新冠病毒（COVID-19）感染。我们的研究对具有中度和重度临床结果的SARS-CoV-2患者的外周血单个核细胞转录组进行了测序，以确定新的潜在宿主受体和生物标志物，这些受体和标志物有助于开发新的转化纳米药物和疫苗疗法。失调的特征与中度和重度患者的体液免疫反应相关，包括B细胞活化、细胞周期紊乱、浆母细胞抗体加工、适应性免疫反应、胞质分裂和白细胞介素信号通路。对中度和重度感染组的比较和纵向分析阐明了调节途径和生物学过程的多样性。在SARS-CoV-2感染患者中，几种免疫球蛋白基因、核糖体蛋白、与炎症反应相关的细胞因子，包括肿瘤坏死因子、C-C基序趋化因子配体、C-X-C基序趋化因子配体以及与细胞周期进程和DNA增殖相关的基因（、和）均显著上调。60S核糖体蛋白L29是所有新冠病毒感染组中高表达的基因。我们的研究表明，基于疾病严重程度和发病情况识别差异表达基因（DEGs）可能是一种强大的方法，用于识别潜在的治疗靶点，以开发针对SARS-CoV-2感染的有效药物递送系统。因此，可以对潜在的治疗靶点，如RPL29蛋白进行测试，以开发未来基于信使核糖核酸（mRNA）的转化纳米药物和疗法来对抗SARS-CoV-2感染。
