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严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的开放阅读框7a(ORF7a)和开放阅读框7b(ORF7b)对抗病毒免疫反应的损害及细胞功能的破坏。

Impairment of antiviral immune response and disruption of cellular functions by SARS-CoV-2 ORF7a and ORF7b.

作者信息

García-García Tránsito, Fernández-Rodríguez Raúl, Redondo Natalia, de Lucas-Rius Ana, Zaldívar-López Sara, López-Ayllón Blanca Dies, Suárez-Cárdenas José M, Jiménez-Marín Ángeles, Montoya María, Garrido Juan J

机构信息

Immunogenomics and Molecular Pathogenesis Group, UIC Zoonoses and Emergent Diseases ENZOEM, Department of Genetics, University of Córdoba, Córdoba, Spain.

Maimónides Biomedical Research Institute of Córdoba (IMIBIC), GA-14 Research Group, Córdoba, Spain.

出版信息

iScience. 2022 Nov 18;25(11):105444. doi: 10.1016/j.isci.2022.105444. Epub 2022 Oct 25.

DOI:10.1016/j.isci.2022.105444
PMID:36310646
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9597514/
Abstract

SARS-CoV-2, the causative agent of the present COVID-19 pandemic, possesses eleven accessory proteins encoded in its genome, and some have been implicated in facilitating infection and pathogenesis through their interaction with cellular components. Among these proteins, accessory protein ORF7a and ORF7b functions are poorly understood. In this study, A549 cells were transduced to express ORF7a and ORF7b, respectively, to explore more in depth the role of each accessory protein in the pathological manifestation leading to COVID-19. Bioinformatic analysis and integration of transcriptome results identified defined canonical pathways and functional groupings revealing that after expression of ORF7a or ORF7b, the lung cells are potentially altered to create conditions more favorable for SARS-CoV-2, by inhibiting the IFN-I response, increasing proinflammatory cytokines release, and altering cell metabolic activity and adhesion. Based on these results, it is plausible to suggest that ORF7a or ORF7b could be used as biomarkers of progression in this pandemic.

摘要

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)是当前新冠疫情的病原体,其基因组编码11种辅助蛋白,其中一些蛋白通过与细胞成分相互作用,被认为在促进感染和发病机制中发挥作用。在这些蛋白中,辅助蛋白ORF7a和ORF7b的功能尚不清楚。在本研究中,分别转导A549细胞以表达ORF7a和ORF7b,以更深入地探究每种辅助蛋白在导致新冠的病理表现中的作用。生物信息学分析和转录组结果整合确定了特定的经典途径和功能分组,结果显示,在表达ORF7a或ORF7b后,肺细胞可能会发生改变,通过抑制I型干扰素反应、增加促炎细胞因子释放以及改变细胞代谢活性和黏附,从而创造更有利于SARS-CoV-2的条件。基于这些结果,有理由认为ORF7a或ORF7b可作为本次疫情进展的生物标志物。

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