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

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...

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Veröffentlicht in:iScience 2022-11, Vol.25 (11), p.105444-105444, Article 105444
Hauptverfasser: 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.
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Sprache:eng
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Zusammenfassung: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. [Display omitted] •Inflammation-related metabolic dysfunctions are induced by ORF7a and ORF7b•ORF7a and ORF7b play key roles in regulating host responses to SARS-CoV-2 infection•ECM-interactions and cell-cell junctions are disrupted by ORF7a or ORF7b•Accessory proteins may create favorable conditions for SARS-CoV-2 infection Immunology; Immune response; Cell biology; Transcriptomics
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2022.105444