SADS-CoV nsp5 Inhibits Interferon Production by Targeting Kinase IKKε

Swine acute diarrhea syndrome coronavirus (SADS-CoV), initially identified in China in February 2017, severely impacts the swine industry by causing lethal watery diarrhea in neonatal piglets. Understanding the molecular mechanism employed by SADS-CoV to evade the host’s immune defenses is of utmost...

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Main Authors: Gaoli She, Chunhui Zhong, Yue Pan, Zexin Chen, Jingmin Li, Mingchong Li, Yufang Liu, Yongchang Cao, Xiaona Wei, Chunyi Xue
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Microorganisms
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Online Access:https://www.mdpi.com/2076-2607/13/7/1494
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author Gaoli She
Chunhui Zhong
Yue Pan
Zexin Chen
Jingmin Li
Mingchong Li
Yufang Liu
Yongchang Cao
Xiaona Wei
Chunyi Xue
author_facet Gaoli She
Chunhui Zhong
Yue Pan
Zexin Chen
Jingmin Li
Mingchong Li
Yufang Liu
Yongchang Cao
Xiaona Wei
Chunyi Xue
author_sort Gaoli She
collection DOAJ
description Swine acute diarrhea syndrome coronavirus (SADS-CoV), initially identified in China in February 2017, severely impacts the swine industry by causing lethal watery diarrhea in neonatal piglets. Understanding the molecular mechanism employed by SADS-CoV to evade the host’s immune defenses is of utmost importance. In this study, using the porcine ileum epithelial cell line IPI-FX as an in vitro model, we investigated the highly pathogenic SADS-CoV GDS04 strain and its nonstructural protein 5 (nsp5) for their roles in inhibiting interferon-beta (IFN-β) production. Our findings indicated that GDS04 inhibited poly(I:C)-induced IFN-β production by impeding the promoter activities of IRF3 and NF-κB. As a 3C-like protease, SADS-CoV nsp5 functioned as an interferon inhibitor by interacting with IKKε, reducing its protein abundance, and inhibiting its phosphorylation. This study enhances our understanding of the interaction between coronaviruses and their hosts, providing novel insights into the evasion of the immune system by coronaviruses.
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institution DOAJ
issn 2076-2607
language English
publishDate 2025-06-01
publisher MDPI AG
record_format Article
series Microorganisms
spelling doaj-art-7bbcfbce4b984539a0712bcfddcd57a92025-08-20T03:08:02ZengMDPI AGMicroorganisms2076-26072025-06-01137149410.3390/microorganisms13071494SADS-CoV nsp5 Inhibits Interferon Production by Targeting Kinase IKKεGaoli She0Chunhui Zhong1Yue Pan2Zexin Chen3Jingmin Li4Mingchong Li5Yufang Liu6Yongchang Cao7Xiaona Wei8Chunyi Xue9State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, ChinaState Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, ChinaState Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, ChinaState Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, ChinaState Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, ChinaState Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, ChinaState Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, ChinaState Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, ChinaState Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, ChinaState Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, ChinaSwine acute diarrhea syndrome coronavirus (SADS-CoV), initially identified in China in February 2017, severely impacts the swine industry by causing lethal watery diarrhea in neonatal piglets. Understanding the molecular mechanism employed by SADS-CoV to evade the host’s immune defenses is of utmost importance. In this study, using the porcine ileum epithelial cell line IPI-FX as an in vitro model, we investigated the highly pathogenic SADS-CoV GDS04 strain and its nonstructural protein 5 (nsp5) for their roles in inhibiting interferon-beta (IFN-β) production. Our findings indicated that GDS04 inhibited poly(I:C)-induced IFN-β production by impeding the promoter activities of IRF3 and NF-κB. As a 3C-like protease, SADS-CoV nsp5 functioned as an interferon inhibitor by interacting with IKKε, reducing its protein abundance, and inhibiting its phosphorylation. This study enhances our understanding of the interaction between coronaviruses and their hosts, providing novel insights into the evasion of the immune system by coronaviruses.https://www.mdpi.com/2076-2607/13/7/1494SADS-CoVGDS04IFN-βnsp5IKKε
spellingShingle Gaoli She
Chunhui Zhong
Yue Pan
Zexin Chen
Jingmin Li
Mingchong Li
Yufang Liu
Yongchang Cao
Xiaona Wei
Chunyi Xue
SADS-CoV nsp5 Inhibits Interferon Production by Targeting Kinase IKKε
Microorganisms
SADS-CoV
GDS04
IFN-β
nsp5
IKKε
title SADS-CoV nsp5 Inhibits Interferon Production by Targeting Kinase IKKε
title_full SADS-CoV nsp5 Inhibits Interferon Production by Targeting Kinase IKKε
title_fullStr SADS-CoV nsp5 Inhibits Interferon Production by Targeting Kinase IKKε
title_full_unstemmed SADS-CoV nsp5 Inhibits Interferon Production by Targeting Kinase IKKε
title_short SADS-CoV nsp5 Inhibits Interferon Production by Targeting Kinase IKKε
title_sort sads cov nsp5 inhibits interferon production by targeting kinase ikkε
topic SADS-CoV
GDS04
IFN-β
nsp5
IKKε
url https://www.mdpi.com/2076-2607/13/7/1494
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