Impairment of antiviral immune response and disruption of cellular functions by SARS-CoV-2 ORF7a and ORF7b
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
Affiliations
Tránsito García-García
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
Raúl Fernández-Rodríguez
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
Natalia Redondo
Molecular Biomedicine Department, Centro de Investigaciones Biológicas Margarita Salas (CIB), CSIC, Madrid 28040, Spain
Ana de Lucas-Rius
Molecular Biomedicine Department, Centro de Investigaciones Biológicas Margarita Salas (CIB), CSIC, Madrid 28040, Spain
Sara Zaldívar-López
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
Blanca Dies López-Ayllón
Molecular Biomedicine Department, Centro de Investigaciones Biológicas Margarita Salas (CIB), CSIC, Madrid 28040, Spain
José M. Suárez-Cárdenas
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
Ángeles Jiménez-Marín
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
María Montoya
Molecular Biomedicine Department, Centro de Investigaciones Biológicas Margarita Salas (CIB), CSIC, Madrid 28040, Spain; Corresponding author
Juan J. Garrido
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; Corresponding author
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.
