Cargando…

SARS-CoV-2 ORF3a positively regulates NF-κB activity by enhancing IKKβ-NEMO interaction

Coronavirus disease 2019 (COVID-19) is a global pandemic caused by SARS-CoV-2 infection. Patients with severe COVID-19 exhibit robust induction of proinflammatory cytokines, which are closely associated with the development of acute respiratory distress syndrome. However, the underlying mechanisms o...

Descripción completa

Detalles Bibliográficos
Autores principales: Nie, Ying, Mou, Lumin, Long, Qizhou, Deng, Dongqing, Hu, Rongying, Cheng, Jinzhi, Wu, Jiahong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10009424/
https://www.ncbi.nlm.nih.gov/pubmed/36894068
http://dx.doi.org/10.1016/j.virusres.2023.199086
_version_ 1784905983144755200
author Nie, Ying
Mou, Lumin
Long, Qizhou
Deng, Dongqing
Hu, Rongying
Cheng, Jinzhi
Wu, Jiahong
author_facet Nie, Ying
Mou, Lumin
Long, Qizhou
Deng, Dongqing
Hu, Rongying
Cheng, Jinzhi
Wu, Jiahong
author_sort Nie, Ying
collection PubMed
description Coronavirus disease 2019 (COVID-19) is a global pandemic caused by SARS-CoV-2 infection. Patients with severe COVID-19 exhibit robust induction of proinflammatory cytokines, which are closely associated with the development of acute respiratory distress syndrome. However, the underlying mechanisms of the NF-κB activation mediated by SARS-CoV-2 infection remain poorly understood. Here, we screened SARS-CoV-2 genes and found that ORF3a induces proinflammatory cytokines by activating the NF-κB pathway. Moreover, we found that ORF3a interacts with IKKβ and NEMO and enhances the interaction of IKKβ-NEMO, thereby positively regulating NF-κB activity. Together, these results suggest ORF3a may play pivotal roles in the pathogenesis of SARS-CoV-2 and provide novel insights into the interaction between host immune responses and SARS-CoV-2 infection.
format Online
Article
Text
id pubmed-10009424
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-100094242023-03-13 SARS-CoV-2 ORF3a positively regulates NF-κB activity by enhancing IKKβ-NEMO interaction Nie, Ying Mou, Lumin Long, Qizhou Deng, Dongqing Hu, Rongying Cheng, Jinzhi Wu, Jiahong Virus Res Article Coronavirus disease 2019 (COVID-19) is a global pandemic caused by SARS-CoV-2 infection. Patients with severe COVID-19 exhibit robust induction of proinflammatory cytokines, which are closely associated with the development of acute respiratory distress syndrome. However, the underlying mechanisms of the NF-κB activation mediated by SARS-CoV-2 infection remain poorly understood. Here, we screened SARS-CoV-2 genes and found that ORF3a induces proinflammatory cytokines by activating the NF-κB pathway. Moreover, we found that ORF3a interacts with IKKβ and NEMO and enhances the interaction of IKKβ-NEMO, thereby positively regulating NF-κB activity. Together, these results suggest ORF3a may play pivotal roles in the pathogenesis of SARS-CoV-2 and provide novel insights into the interaction between host immune responses and SARS-CoV-2 infection. Elsevier 2023-03-13 /pmc/articles/PMC10009424/ /pubmed/36894068 http://dx.doi.org/10.1016/j.virusres.2023.199086 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Nie, Ying
Mou, Lumin
Long, Qizhou
Deng, Dongqing
Hu, Rongying
Cheng, Jinzhi
Wu, Jiahong
SARS-CoV-2 ORF3a positively regulates NF-κB activity by enhancing IKKβ-NEMO interaction
title SARS-CoV-2 ORF3a positively regulates NF-κB activity by enhancing IKKβ-NEMO interaction
title_full SARS-CoV-2 ORF3a positively regulates NF-κB activity by enhancing IKKβ-NEMO interaction
title_fullStr SARS-CoV-2 ORF3a positively regulates NF-κB activity by enhancing IKKβ-NEMO interaction
title_full_unstemmed SARS-CoV-2 ORF3a positively regulates NF-κB activity by enhancing IKKβ-NEMO interaction
title_short SARS-CoV-2 ORF3a positively regulates NF-κB activity by enhancing IKKβ-NEMO interaction
title_sort sars-cov-2 orf3a positively regulates nf-κb activity by enhancing ikkβ-nemo interaction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10009424/
https://www.ncbi.nlm.nih.gov/pubmed/36894068
http://dx.doi.org/10.1016/j.virusres.2023.199086
work_keys_str_mv AT nieying sarscov2orf3apositivelyregulatesnfkbactivitybyenhancingikkbnemointeraction
AT moulumin sarscov2orf3apositivelyregulatesnfkbactivitybyenhancingikkbnemointeraction
AT longqizhou sarscov2orf3apositivelyregulatesnfkbactivitybyenhancingikkbnemointeraction
AT dengdongqing sarscov2orf3apositivelyregulatesnfkbactivitybyenhancingikkbnemointeraction
AT hurongying sarscov2orf3apositivelyregulatesnfkbactivitybyenhancingikkbnemointeraction
AT chengjinzhi sarscov2orf3apositivelyregulatesnfkbactivitybyenhancingikkbnemointeraction
AT wujiahong sarscov2orf3apositivelyregulatesnfkbactivitybyenhancingikkbnemointeraction