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SARS-CoV-2 accessory proteins involvement in inflammatory and profibrotic processes through IL11 signaling

SARS-CoV-2, the cause of the COVID-19 pandemic, possesses eleven accessory proteins encoded in its genome. Their roles during infection are still not completely understood. In this study, transcriptomics analysis revealed that both WNT5A and IL11 were significantly up-regulated in A549 cells express...

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Autores principales: López-Ayllón, Blanca D., de Lucas-Rius, Ana, Mendoza-García, Laura, García-García, Tránsito, Fernández-Rodríguez, Raúl, Suárez-Cárdenas, José M., Santos, Fátima Milhano, Corrales, Fernando, Redondo, Natalia, Pedrucci, Federica, Zaldívar-López, Sara, Jiménez-Marín, Ángeles, Garrido, Juan J., Montoya, María
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10399023/
https://www.ncbi.nlm.nih.gov/pubmed/37545510
http://dx.doi.org/10.3389/fimmu.2023.1220306
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author López-Ayllón, Blanca D.
de Lucas-Rius, Ana
Mendoza-García, Laura
García-García, Tránsito
Fernández-Rodríguez, Raúl
Suárez-Cárdenas, José M.
Santos, Fátima Milhano
Corrales, Fernando
Redondo, Natalia
Pedrucci, Federica
Zaldívar-López, Sara
Jiménez-Marín, Ángeles
Garrido, Juan J.
Montoya, María
author_facet López-Ayllón, Blanca D.
de Lucas-Rius, Ana
Mendoza-García, Laura
García-García, Tránsito
Fernández-Rodríguez, Raúl
Suárez-Cárdenas, José M.
Santos, Fátima Milhano
Corrales, Fernando
Redondo, Natalia
Pedrucci, Federica
Zaldívar-López, Sara
Jiménez-Marín, Ángeles
Garrido, Juan J.
Montoya, María
author_sort López-Ayllón, Blanca D.
collection PubMed
description SARS-CoV-2, the cause of the COVID-19 pandemic, possesses eleven accessory proteins encoded in its genome. Their roles during infection are still not completely understood. In this study, transcriptomics analysis revealed that both WNT5A and IL11 were significantly up-regulated in A549 cells expressing individual accessory proteins ORF6, ORF8, ORF9b or ORF9c from SARS-CoV-2 (Wuhan-Hu-1 isolate). IL11 is a member of the IL6 family of cytokines. IL11 signaling-related genes were also differentially expressed. Bioinformatics analysis disclosed that both WNT5A and IL11 were involved in pulmonary fibrosis idiopathic disease and functional assays confirmed their association with profibrotic cell responses. Subsequently, data comparison with lung cell lines infected with SARS-CoV-2 or lung biopsies from patients with COVID-19, evidenced altered profibrotic gene expression that matched those obtained in this study. Our results show ORF6, ORF8, ORF9b and ORF9c involvement in inflammatory and profibrotic responses. Thus, these accessory proteins could be targeted by new therapies against COVID-19 disease.
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spelling pubmed-103990232023-08-04 SARS-CoV-2 accessory proteins involvement in inflammatory and profibrotic processes through IL11 signaling López-Ayllón, Blanca D. de Lucas-Rius, Ana Mendoza-García, Laura García-García, Tránsito Fernández-Rodríguez, Raúl Suárez-Cárdenas, José M. Santos, Fátima Milhano Corrales, Fernando Redondo, Natalia Pedrucci, Federica Zaldívar-López, Sara Jiménez-Marín, Ángeles Garrido, Juan J. Montoya, María Front Immunol Immunology SARS-CoV-2, the cause of the COVID-19 pandemic, possesses eleven accessory proteins encoded in its genome. Their roles during infection are still not completely understood. In this study, transcriptomics analysis revealed that both WNT5A and IL11 were significantly up-regulated in A549 cells expressing individual accessory proteins ORF6, ORF8, ORF9b or ORF9c from SARS-CoV-2 (Wuhan-Hu-1 isolate). IL11 is a member of the IL6 family of cytokines. IL11 signaling-related genes were also differentially expressed. Bioinformatics analysis disclosed that both WNT5A and IL11 were involved in pulmonary fibrosis idiopathic disease and functional assays confirmed their association with profibrotic cell responses. Subsequently, data comparison with lung cell lines infected with SARS-CoV-2 or lung biopsies from patients with COVID-19, evidenced altered profibrotic gene expression that matched those obtained in this study. Our results show ORF6, ORF8, ORF9b and ORF9c involvement in inflammatory and profibrotic responses. Thus, these accessory proteins could be targeted by new therapies against COVID-19 disease. Frontiers Media S.A. 2023-07-20 /pmc/articles/PMC10399023/ /pubmed/37545510 http://dx.doi.org/10.3389/fimmu.2023.1220306 Text en Copyright © 2023 López-Ayllón, de Lucas-Rius, Mendoza-García, García-García, Fernández-Rodríguez, Suárez-Cárdenas, Santos, Corrales, Redondo, Pedrucci, Zaldívar-López, Jiménez-Marín, Garrido and Montoya https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
López-Ayllón, Blanca D.
de Lucas-Rius, Ana
Mendoza-García, Laura
García-García, Tránsito
Fernández-Rodríguez, Raúl
Suárez-Cárdenas, José M.
Santos, Fátima Milhano
Corrales, Fernando
Redondo, Natalia
Pedrucci, Federica
Zaldívar-López, Sara
Jiménez-Marín, Ángeles
Garrido, Juan J.
Montoya, María
SARS-CoV-2 accessory proteins involvement in inflammatory and profibrotic processes through IL11 signaling
title SARS-CoV-2 accessory proteins involvement in inflammatory and profibrotic processes through IL11 signaling
title_full SARS-CoV-2 accessory proteins involvement in inflammatory and profibrotic processes through IL11 signaling
title_fullStr SARS-CoV-2 accessory proteins involvement in inflammatory and profibrotic processes through IL11 signaling
title_full_unstemmed SARS-CoV-2 accessory proteins involvement in inflammatory and profibrotic processes through IL11 signaling
title_short SARS-CoV-2 accessory proteins involvement in inflammatory and profibrotic processes through IL11 signaling
title_sort sars-cov-2 accessory proteins involvement in inflammatory and profibrotic processes through il11 signaling
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10399023/
https://www.ncbi.nlm.nih.gov/pubmed/37545510
http://dx.doi.org/10.3389/fimmu.2023.1220306
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