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

Summary: 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 O...

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Main Authors: Tránsito García-García, Raúl Fernández-Rodríguez, Natalia Redondo, Ana de Lucas-Rius, Sara Zaldívar-López, Blanca Dies López-Ayllón, José M. Suárez-Cárdenas, Ángeles Jiménez-Marín, María Montoya, Juan J. Garrido
Format: Article
Language:English
Published: Elsevier 2022-11-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004222017163
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author Tránsito García-García
Raúl Fernández-Rodríguez
Natalia Redondo
Ana de Lucas-Rius
Sara Zaldívar-López
Blanca Dies López-Ayllón
José M. Suárez-Cárdenas
Ángeles Jiménez-Marín
María Montoya
Juan J. Garrido
author_facet Tránsito García-García
Raúl Fernández-Rodríguez
Natalia Redondo
Ana de Lucas-Rius
Sara Zaldívar-López
Blanca Dies López-Ayllón
José M. Suárez-Cárdenas
Ángeles Jiménez-Marín
María Montoya
Juan J. Garrido
author_sort Tránsito García-García
collection DOAJ
description Summary: 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.
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spelling doaj.art-9a13bebe61cf4759bf74166f3e5e5a672022-12-22T04:11:31ZengElsevieriScience2589-00422022-11-012511105444Impairment of antiviral immune response and disruption of cellular functions by SARS-CoV-2 ORF7a and ORF7bTránsito García-García0Raúl Fernández-Rodríguez1Natalia Redondo2Ana de Lucas-Rius3Sara Zaldívar-López4Blanca Dies López-Ayllón5José M. Suárez-Cárdenas6Ángeles Jiménez-Marín7María Montoya8Juan J. Garrido9Immunogenomics 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, SpainImmunogenomics 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, SpainMolecular Biomedicine Department, Centro de Investigaciones Biológicas Margarita Salas (CIB), CSIC, Madrid 28040, SpainMolecular Biomedicine Department, Centro de Investigaciones Biológicas Margarita Salas (CIB), CSIC, Madrid 28040, SpainImmunogenomics 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, SpainMolecular Biomedicine Department, Centro de Investigaciones Biológicas Margarita Salas (CIB), CSIC, Madrid 28040, SpainImmunogenomics 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, SpainImmunogenomics 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, SpainMolecular Biomedicine Department, Centro de Investigaciones Biológicas Margarita Salas (CIB), CSIC, Madrid 28040, Spain; Corresponding authorImmunogenomics 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; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004222017163ImmunologyImmune responseCell biologyTranscriptomics
spellingShingle Tránsito García-García
Raúl Fernández-Rodríguez
Natalia Redondo
Ana de Lucas-Rius
Sara Zaldívar-López
Blanca Dies López-Ayllón
José M. Suárez-Cárdenas
Ángeles Jiménez-Marín
María Montoya
Juan J. Garrido
Impairment of antiviral immune response and disruption of cellular functions by SARS-CoV-2 ORF7a and ORF7b
iScience
Immunology
Immune response
Cell biology
Transcriptomics
title Impairment of antiviral immune response and disruption of cellular functions by SARS-CoV-2 ORF7a and ORF7b
title_full Impairment of antiviral immune response and disruption of cellular functions by SARS-CoV-2 ORF7a and ORF7b
title_fullStr Impairment of antiviral immune response and disruption of cellular functions by SARS-CoV-2 ORF7a and ORF7b
title_full_unstemmed Impairment of antiviral immune response and disruption of cellular functions by SARS-CoV-2 ORF7a and ORF7b
title_short Impairment of antiviral immune response and disruption of cellular functions by SARS-CoV-2 ORF7a and ORF7b
title_sort impairment of antiviral immune response and disruption of cellular functions by sars cov 2 orf7a and orf7b
topic Immunology
Immune response
Cell biology
Transcriptomics
url http://www.sciencedirect.com/science/article/pii/S2589004222017163
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