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...
Autores principales: | , , , , , , |
---|---|
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 |