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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...

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Autores principales: Kaewborisuth, Challika, Koonpaew, Surapong, Srisutthisamphan, Kanjana, Viriyakitkosol, Ratchanont, Jaru-ampornpan, Peera, Jongkaewwattana, Anan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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