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新冠病毒住院患者中不同预后的严重急性呼吸综合征冠状病毒2开放阅读框7亚基因组RNA与宿主干扰素-β表达

SARS-CoV-2 ORF7 subgenomic RNA and Host IFN-β Expression in COVID-19 Hospitalized Patients with Different Prognosis.

作者信息

Zirakjou Akbar, Sadeghi Farzin, Ebrahimian Shiadeh Arefeh, Hatamibardar Maryam, Ranaee Mohammad, Gholinia Hemmat, Ghorbani Hossein

机构信息

Student Research Committee, Babol University of Medical Sciences, Babol, Iran.

Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.

出版信息

Int J Mol Cell Med. 2025 Jul 1;14(2):726-735. doi: 10.22088/IJMCM.BUMS.14.2.726. eCollection 2025.

Abstract

The worldwide spread of COVID-19, triggered by SARS-CoV-2, has highlighted how viral accessory proteins contribute significantly to bypassing host immune defenses and increasing illness severity. This study investigates the relationship between the levels of SARS-CoV-2 subgenomic RNA (sgRNA) for ORF7a and ORF7b and host interferon-beta (IFN-β) expression in hospitalized COVID-19 patients with different prognoses. Upper respiratory tract samples from 89 patients (49 with poor prognosis and 40 with good prognosis) were analyzed using quantitative real-time PCR to measure ORF7a, ORF7b, and IFN-β expression levels. The results revealed significantly higher expression of ORF7a and ORF7b in patients with poor prognosis compared to those with favorable outcomes (P < 0.001). Conversely, IFN-β expression was significantly reduced in the poor prognosis group (P < 0.001), suggesting a potential mechanism of immune suppression. Older age, underlying health conditions, and elevated levels of inflammatory biomarkers, such as CRP and D-dimer, were also associated with poorer outcomes. These findings underscore the potential role of ORF7 proteins in suppressing IFN-β signaling, contributing to disease severity. Targeting these viral proteins may offer promising therapeutic avenues to enhance antiviral responses and improve patient outcomes. The study was conducted from August 2022 to February 2022. Further research is warranted to better understand the interplay between viral immune evasion mechanisms and host responses across diverse patient populations.

摘要

由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引发的新冠病毒病(COVID-19)在全球范围内的传播,凸显了病毒辅助蛋白在显著绕过宿主免疫防御并增加疾病严重程度方面所起的作用。本研究调查了不同预后的住院COVID-19患者中,开放阅读框7a(ORF7a)和开放阅读框7b(ORF7b)的严重急性呼吸综合征冠状病毒2亚基因组RNA(sgRNA)水平与宿主干扰素-β(IFN-β)表达之间的关系。使用定量实时聚合酶链反应(PCR)分析了89例患者(49例预后不良,40例预后良好)的上呼吸道样本,以测量ORF7a、ORF7b和IFN-β的表达水平。结果显示,与预后良好的患者相比,预后不良的患者中ORF7a和ORF7b的表达显著更高(P < 0.001)。相反,预后不良组的IFN-β表达显著降低(P < 0.001),提示存在免疫抑制的潜在机制。年龄较大、有基础健康状况以及炎症生物标志物(如C反应蛋白和D-二聚体)水平升高也与较差的预后相关。这些发现强调了ORF7蛋白在抑制IFN-β信号传导、导致疾病严重程度方面的潜在作用。靶向这些病毒蛋白可能为增强抗病毒反应和改善患者预后提供有前景的治疗途径。该研究于2022年8月至2022年2月进行。有必要进行进一步研究,以更好地了解病毒免疫逃逸机制与不同患者群体宿主反应之间的相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5edb/12321312/018e4c0e9dea/ijmcm-14-2-726-g001.jpg

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