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PEDV ORF3 Independently Regulates IκB Kinase β-Mediated NF-κB and IFN-β Promoter Activities
The Open Reading Frame 3 (ORF3), an accessory protein of porcine epidemic diarrhea virus (PEDV), has been shown to interact with a myriad of cellular proteins, among which include the IκB kinase β (IKBKB). Here, specific IKBKB domains responsible for ORF3–IKBKB interaction were identified. Dysregula...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281231/ https://www.ncbi.nlm.nih.gov/pubmed/32423021 http://dx.doi.org/10.3390/pathogens9050376 |
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author | Kaewborisuth, Challika Koonpaew, Surapong Srisutthisamphan, Kanjana Viriyakitkosol, Ratchanont Jaru-ampornpan, Peera Jongkaewwattana, Anan |
author_facet | Kaewborisuth, Challika Koonpaew, Surapong Srisutthisamphan, Kanjana Viriyakitkosol, Ratchanont Jaru-ampornpan, Peera Jongkaewwattana, Anan |
author_sort | Kaewborisuth, Challika |
collection | PubMed |
description | The Open Reading Frame 3 (ORF3), an accessory protein of porcine epidemic diarrhea virus (PEDV), has been shown to interact with a myriad of cellular proteins, among which include the IκB kinase β (IKBKB). Here, specific IKBKB domains responsible for ORF3–IKBKB interaction were identified. Dysregulation of NF-κB and Type I interferon (IFN) in the presence of ORF3 was also demonstrated. We showed that while ORF3 was capable of up-regulating IKBKB-meditated NF-κB promoter activity, it surprisingly down-regulated the activation of IKBKB-meditated IFN-β promoter and expression of IFN-β mRNA. When overexpressed, ORF3 could suppress Poly I:C mediated type I IFN production and induction. Finally, we demonstrated that IKBKB- and RIG-I-mediated type I IFN induction by ORF3 resulted in different outcomes. Our study is the first to demonstrate the potential and complex roles of ORF3 in the involvement of aberrant immune signaling as well as in the virus–host interaction. |
format | Online Article Text |
id | pubmed-7281231 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72812312020-06-15 PEDV ORF3 Independently Regulates IκB Kinase β-Mediated NF-κB and IFN-β Promoter Activities Kaewborisuth, Challika Koonpaew, Surapong Srisutthisamphan, Kanjana Viriyakitkosol, Ratchanont Jaru-ampornpan, Peera Jongkaewwattana, Anan Pathogens Article The Open Reading Frame 3 (ORF3), an accessory protein of porcine epidemic diarrhea virus (PEDV), has been shown to interact with a myriad of cellular proteins, among which include the IκB kinase β (IKBKB). Here, specific IKBKB domains responsible for ORF3–IKBKB interaction were identified. Dysregulation of NF-κB and Type I interferon (IFN) in the presence of ORF3 was also demonstrated. We showed that while ORF3 was capable of up-regulating IKBKB-meditated NF-κB promoter activity, it surprisingly down-regulated the activation of IKBKB-meditated IFN-β promoter and expression of IFN-β mRNA. When overexpressed, ORF3 could suppress Poly I:C mediated type I IFN production and induction. Finally, we demonstrated that IKBKB- and RIG-I-mediated type I IFN induction by ORF3 resulted in different outcomes. Our study is the first to demonstrate the potential and complex roles of ORF3 in the involvement of aberrant immune signaling as well as in the virus–host interaction. MDPI 2020-05-14 /pmc/articles/PMC7281231/ /pubmed/32423021 http://dx.doi.org/10.3390/pathogens9050376 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kaewborisuth, Challika Koonpaew, Surapong Srisutthisamphan, Kanjana Viriyakitkosol, Ratchanont Jaru-ampornpan, Peera Jongkaewwattana, Anan PEDV ORF3 Independently Regulates IκB Kinase β-Mediated NF-κB and IFN-β Promoter Activities |
title | PEDV ORF3 Independently Regulates IκB Kinase β-Mediated NF-κB and IFN-β Promoter Activities |
title_full | PEDV ORF3 Independently Regulates IκB Kinase β-Mediated NF-κB and IFN-β Promoter Activities |
title_fullStr | PEDV ORF3 Independently Regulates IκB Kinase β-Mediated NF-κB and IFN-β Promoter Activities |
title_full_unstemmed | PEDV ORF3 Independently Regulates IκB Kinase β-Mediated NF-κB and IFN-β Promoter Activities |
title_short | PEDV ORF3 Independently Regulates IκB Kinase β-Mediated NF-κB and IFN-β Promoter Activities |
title_sort | pedv orf3 independently regulates iκb kinase β-mediated nf-κb and ifn-β promoter activities |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281231/ https://www.ncbi.nlm.nih.gov/pubmed/32423021 http://dx.doi.org/10.3390/pathogens9050376 |
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