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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MDPI AG
2020-05-01
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Online Access: | https://www.mdpi.com/2076-0817/9/5/376 |
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author | Challika Kaewborisuth Surapong Koonpaew Kanjana Srisutthisamphan Ratchanont Viriyakitkosol Peera Jaru-ampornpan Anan Jongkaewwattana |
author_facet | Challika Kaewborisuth Surapong Koonpaew Kanjana Srisutthisamphan Ratchanont Viriyakitkosol Peera Jaru-ampornpan Anan Jongkaewwattana |
author_sort | Challika Kaewborisuth |
collection | DOAJ |
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. |
first_indexed | 2024-03-10T19:49:28Z |
format | Article |
id | doaj.art-44b84484c1dd4af2b8962c4918c71e35 |
institution | Directory Open Access Journal |
issn | 2076-0817 |
language | English |
last_indexed | 2024-03-10T19:49:28Z |
publishDate | 2020-05-01 |
publisher | MDPI AG |
record_format | Article |
series | Pathogens |
spelling | doaj.art-44b84484c1dd4af2b8962c4918c71e352023-11-20T00:27:29ZengMDPI AGPathogens2076-08172020-05-019537610.3390/pathogens9050376PEDV ORF3 Independently Regulates IκB Kinase β-Mediated NF-κB and IFN-β Promoter ActivitiesChallika Kaewborisuth0Surapong Koonpaew1Kanjana Srisutthisamphan2Ratchanont Viriyakitkosol3Peera Jaru-ampornpan4Anan Jongkaewwattana5Virology and Cell Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani 12120, ThailandVirology and Cell Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani 12120, ThailandVirology and Cell Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani 12120, ThailandFaculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, ThailandVirology and Cell Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani 12120, ThailandVirology and Cell Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani 12120, ThailandThe 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.https://www.mdpi.com/2076-0817/9/5/376ORF3Porcine epidemic diarrhea virusIKBKBNF-κBIFN-βType I IFN induction |
spellingShingle | Challika Kaewborisuth Surapong Koonpaew Kanjana Srisutthisamphan Ratchanont Viriyakitkosol Peera Jaru-ampornpan Anan Jongkaewwattana PEDV ORF3 Independently Regulates IκB Kinase β-Mediated NF-κB and IFN-β Promoter Activities Pathogens ORF3 Porcine epidemic diarrhea virus IKBKB NF-κB IFN-β Type I IFN induction |
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 | ORF3 Porcine epidemic diarrhea virus IKBKB NF-κB IFN-β Type I IFN induction |
url | https://www.mdpi.com/2076-0817/9/5/376 |
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