Optineurin negatively regulates the induction of IFNbeta in response to RNA virus infection.

The innate immune response provides a critical defense against microbial infections, including viruses. These are recognised by pattern recognition receptors including Toll-like receptors (TLRs) and RIG-I like helicases (RLHs). Detection of virus triggers signalling cascades that induce transcriptio...

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Autores principales:	Jamel Mankouri, Rennos Fragkoudis, Kathryn H Richards, Laura F Wetherill, Mark Harris, Alain Kohl, Richard M Elliott, Andrew Macdonald
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8b1cdff4e5f94af59bc041f47ac7542d
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spelling	oai:doaj.org-article:8b1cdff4e5f94af59bc041f47ac7542d2021-11-25T05:48:17ZOptineurin negatively regulates the induction of IFNbeta in response to RNA virus infection.1553-73661553-737410.1371/journal.ppat.1000778https://doaj.org/article/8b1cdff4e5f94af59bc041f47ac7542d2010-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20174559/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The innate immune response provides a critical defense against microbial infections, including viruses. These are recognised by pattern recognition receptors including Toll-like receptors (TLRs) and RIG-I like helicases (RLHs). Detection of virus triggers signalling cascades that induce transcription of type I interferons including IFNbeta, which are pivotal for the initiation of an anti-viral state. Despite the essential role of IFNbeta in the anti-viral response, there is an incomplete understanding of the negative regulation of IFNbeta induction. Here we provide evidence that expression of the Nemo-related protein, optineurin (NRP/FIP2), has a role in the inhibition of virus-triggered IFNbeta induction. Over-expression of optineurin inhibited Sendai-virus (SeV) and dsRNA triggered induction of IFNbeta, whereas depletion of optineurin with siRNA promoted virus-induced IFNbeta production and decreased RNA virus replication. Immunoprecipitation and immunofluorescence studies identified optineurin in a protein complex containing the antiviral protein kinase TBK1 and the ubiquitin ligase TRAF3. Furthermore, mutagenesis studies determined that binding of ubiquitin was essential for both the correct sub-cellular localisation and the inhibitory function of optineurin. This work identifies optineurin as a critical regulator of antiviral signalling and potential target for future antiviral therapy.Jamel MankouriRennos FragkoudisKathryn H RichardsLaura F WetherillMark HarrisAlain KohlRichard M ElliottAndrew MacdonaldPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 2, p e1000778 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Jamel Mankouri Rennos Fragkoudis Kathryn H Richards Laura F Wetherill Mark Harris Alain Kohl Richard M Elliott Andrew Macdonald Optineurin negatively regulates the induction of IFNbeta in response to RNA virus infection.
description	The innate immune response provides a critical defense against microbial infections, including viruses. These are recognised by pattern recognition receptors including Toll-like receptors (TLRs) and RIG-I like helicases (RLHs). Detection of virus triggers signalling cascades that induce transcription of type I interferons including IFNbeta, which are pivotal for the initiation of an anti-viral state. Despite the essential role of IFNbeta in the anti-viral response, there is an incomplete understanding of the negative regulation of IFNbeta induction. Here we provide evidence that expression of the Nemo-related protein, optineurin (NRP/FIP2), has a role in the inhibition of virus-triggered IFNbeta induction. Over-expression of optineurin inhibited Sendai-virus (SeV) and dsRNA triggered induction of IFNbeta, whereas depletion of optineurin with siRNA promoted virus-induced IFNbeta production and decreased RNA virus replication. Immunoprecipitation and immunofluorescence studies identified optineurin in a protein complex containing the antiviral protein kinase TBK1 and the ubiquitin ligase TRAF3. Furthermore, mutagenesis studies determined that binding of ubiquitin was essential for both the correct sub-cellular localisation and the inhibitory function of optineurin. This work identifies optineurin as a critical regulator of antiviral signalling and potential target for future antiviral therapy.
format	article
author	Jamel Mankouri Rennos Fragkoudis Kathryn H Richards Laura F Wetherill Mark Harris Alain Kohl Richard M Elliott Andrew Macdonald
author_facet	Jamel Mankouri Rennos Fragkoudis Kathryn H Richards Laura F Wetherill Mark Harris Alain Kohl Richard M Elliott Andrew Macdonald
author_sort	Jamel Mankouri
title	Optineurin negatively regulates the induction of IFNbeta in response to RNA virus infection.
title_short	Optineurin negatively regulates the induction of IFNbeta in response to RNA virus infection.
title_full	Optineurin negatively regulates the induction of IFNbeta in response to RNA virus infection.
title_fullStr	Optineurin negatively regulates the induction of IFNbeta in response to RNA virus infection.
title_full_unstemmed	Optineurin negatively regulates the induction of IFNbeta in response to RNA virus infection.
title_sort	optineurin negatively regulates the induction of ifnbeta in response to rna virus infection.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/8b1cdff4e5f94af59bc041f47ac7542d
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Optineurin negatively regulates the induction of IFNbeta in response to RNA virus infection.

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