About: Porcine Reproductive and Respiratory Syndrome Virus nsp11 Antagonizes Type I Interferon Signaling by Targeting IRF9

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Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Porcine Reproductive and Respiratory Syndrome Virus nsp11 Antagonizes Type I Interferon Signaling by Targeting IRF9
Creator	Fang, Liurong Wang, Dang Xiao, Shaobo Zhu, Xinyu Chen, Jiyao Xu, Shangen Yu, Chaoliang Wang, Citation
source	Medline; PMC
abstract	Porcine reproductive and respiratory syndrome virus (PRRSV) is an arterivirus from the Nidovirales order that causes reproductive failure and respiratory disease in pigs and poses a constant threat to the global pig industry. The PRRSV-encoded nonstructural protein 11 (nsp11) is a nidovirus-specific endoribonuclease (NendoU) that is conserved throughout the Arteriviridae and Coronaviridae families. Previously, our research and that of others demonstrated that PRRSV nsp11 inhibits type I interferon (IFN) production through NendoU activity-dependent mechanisms. Here, we found that PRRSV nsp11 also inhibited IFN-stimulated response element (ISRE) promoter activity and subsequent transcription of IFN-stimulated genes (ISGs). Detailed analysis showed that nsp11 targeted interferon regulatory factor 9 (IRF9), but not transducer and activator of transcription 1 (STAT1) or STAT2, key molecules in the type I IFN signaling pathway. Furthermore, the nsp11-IRF9 interaction impaired the formation and nuclear translocation of the transcription factor complex IFN-stimulated gene factor 3 (ISGF3) in both nsp11-overexpressed and PRRSV-infected cells. Importantly, nsp11 mutations (H129A, H144A, and K173A) that ablate NendoU activity or its cell cytotoxicity also interacted with IRF9 and retained the ability to block IFN signaling, indicating that the nsp11-IRF9 interaction is independent of NendoU activity or cell cytotoxicity of nsp11. Taking the results together, our study demonstrated that PRRSV nsp11 antagonizes type I IFN signaling by targeting IRF9 via a NendoU activity-independent mechanism, and this report describes a novel strategy evolved by PRRSV to counteract host innate antiviral responses, revealing a potential new function for PRRSV nsp11 in type I IFN signaling. IMPORTANCE The nidovirus-specific endoribonuclease (NendoU) encoded by PRRSV nonstructural protein 11 (nsp11) is a unique NendoU of nidoviruses that infect vertebrates; thus, it is an attractive target for the development of antinidovirus drugs. Previous studies have revealed that the NendoU of nidoviruses, including porcine reproductive and respiratory syndrome virus (PRRSV) and human coronavirus 229E (HCoV-229E), acts as a type I interferon (IFN) antagonist. Here, for the first time, we demonstrated that overexpression of PRRSV nsp11 also inhibits IFN signaling by targeting the C-terminal interferon regulatory factor (IRF) association domain of IRF9. This interaction impaired the ability of IRF9 to form the transcription factor complex IFN-stimulated gene factor 3 (ISGF3) and to act as a signaling protein of IFN signaling. Collectively, our data identify IRF9 as a natural target of PRRSV NendoU and reveal a novel mechanism evolved by an arterivirus to counteract innate immune signaling.
has issue date	2019-05-15(xsd:dateTime)
bibo:doi	10.1128/jvi.00623-19
bibo:pmid	31092569
has license	bronze-oa
sha1sum (hex)	cbc6fcee006fd6fe5719f4f33ff26ef3f763b6e8
schema:url	https://doi.org/10.1128/jvi.00623-19
resource representing a document's title	Porcine Reproductive and Respiratory Syndrome Virus nsp11 Antagonizes Type I Interferon Signaling by Targeting IRF9
has PubMed Central identifier	PMC6639278
has PubMed identifier	31092569
schema:publication	Journal of Virology
resource representing a document's body	covid:cbc6fcee006fd6fe5719f4f33ff26ef3f763b6e8#body_text
is schema:about of	named entity 'revealed' named entity 'interaction' named entity 'antagonizes' named entity 'factor' named entity 'respiratory disease' named entity 'virus' named entity 'Here' named entity 'signaling' named entity 'signaling pathway' named entity 'transcription' named entity 'acts' named entity 'block' named entity 'NEW' named entity 'ACTIVATOR OF' named entity 'ASSOCIATION' named entity 'PROMOTER ACTIVITY' named entity 'ORDER' named entity 'STAT2' named entity 'PREVIOUS' named entity 'RESULTS' named entity 'STRATEGY' named entity 'SUBSEQUENT' named entity 'REVEALING' named entity 'POTENTIAL' named entity 'INDICATING' named entity 'BUT' named entity 'TYPE I INTERFERON' named entity 'INTERFERON SIGNALING' named entity 'TARGETING' named entity 'CELL' named entity 'signaling' named entity 'ability' named entity 'virus' named entity 'production' named entity 'transcription factor' named entity 'key' named entity 'responses' named entity 'families' named entity 'cell' named entity 'strategy' named entity 'targeting' named entity 'time' named entity 'innate' named entity 'studies' named entity 'target' named entity 'Signaling' named entity 'Syndrome' named entity 'nidoviruses' named entity 'IFN' named entity '229E' named entity 'arterivirus' named entity 'Nidovirales' named entity 'type I IFN' named entity 'ISGs' named entity 'porcine reproductive and respiratory syndrome virus' named entity 'cytotoxicity' named entity 'interferon regulatory factor' named entity 'IRF9' named entity 'Porcine Reproductive and Respiratory Syndrome Virus' named entity 'IRF9' named entity 'Porcine' named entity 'factor' named entity 'cytoplasmic' named entity 'nsp4' named entity 'China' named entity 'STAT2' named entity 'reverse transcribed' named entity 'ISG15' named entity 'viruses' named entity 'luciferase' named entity 'IFN' named entity 'Western blotting' named entity 'tyrosine kinases' named entity 'nsp2'

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