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Rotavirus NSP1 Inhibits Type I and Type III Interferon Induction

Type I interferons (IFNs) are produced by most cells in response to virus infection and stimulate a program of anti-viral gene expression in neighboring cells to suppress virus replication. Type III IFNs have similar properties, however their effects are limited to epithelial cells at mucosal surfac...

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Autores principales: Iaconis, Gennaro, Jackson, Ben, Childs, Kay, Boyce, Mark, Goodbourn, Stephen, Blake, Neil, Iturriza-Gomara, Miren, Seago, Julian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066714/
https://www.ncbi.nlm.nih.gov/pubmed/33807175
http://dx.doi.org/10.3390/v13040589
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author Iaconis, Gennaro
Jackson, Ben
Childs, Kay
Boyce, Mark
Goodbourn, Stephen
Blake, Neil
Iturriza-Gomara, Miren
Seago, Julian
author_facet Iaconis, Gennaro
Jackson, Ben
Childs, Kay
Boyce, Mark
Goodbourn, Stephen
Blake, Neil
Iturriza-Gomara, Miren
Seago, Julian
author_sort Iaconis, Gennaro
collection PubMed
description Type I interferons (IFNs) are produced by most cells in response to virus infection and stimulate a program of anti-viral gene expression in neighboring cells to suppress virus replication. Type III IFNs have similar properties, however their effects are limited to epithelial cells at mucosal surfaces due to restricted expression of the type III IFN receptor. Rotavirus (RV) replicates in intestinal epithelial cells that respond predominantly to type III IFNs, and it has been shown that type III rather than type I IFNs are important for controlling RV infections in vivo. The RV NSP1 protein antagonizes the host type I IFN response by targeting IRF-3, IRF-5, IRF-7, or β-TrCP for proteasome-mediated degradation in a strain-specific manner. Here we provide the first demonstration that NSP1 proteins from several human and animal RV strains antagonize type III as well as type I IFN induction. We also show that NSP1 is a potent inhibitor of IRF-1, a previously undescribed property of NSP1 which is conserved among human and animal RVs. Interestingly, all NSP1 proteins were substantially more effective inhibitors of IRF-1 than either IRF-3 or IRF-7 which has significance for evasion of basal anti-viral immunity and type III IFN induction in the intestinal epithelium.
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spelling pubmed-80667142021-04-25 Rotavirus NSP1 Inhibits Type I and Type III Interferon Induction Iaconis, Gennaro Jackson, Ben Childs, Kay Boyce, Mark Goodbourn, Stephen Blake, Neil Iturriza-Gomara, Miren Seago, Julian Viruses Article Type I interferons (IFNs) are produced by most cells in response to virus infection and stimulate a program of anti-viral gene expression in neighboring cells to suppress virus replication. Type III IFNs have similar properties, however their effects are limited to epithelial cells at mucosal surfaces due to restricted expression of the type III IFN receptor. Rotavirus (RV) replicates in intestinal epithelial cells that respond predominantly to type III IFNs, and it has been shown that type III rather than type I IFNs are important for controlling RV infections in vivo. The RV NSP1 protein antagonizes the host type I IFN response by targeting IRF-3, IRF-5, IRF-7, or β-TrCP for proteasome-mediated degradation in a strain-specific manner. Here we provide the first demonstration that NSP1 proteins from several human and animal RV strains antagonize type III as well as type I IFN induction. We also show that NSP1 is a potent inhibitor of IRF-1, a previously undescribed property of NSP1 which is conserved among human and animal RVs. Interestingly, all NSP1 proteins were substantially more effective inhibitors of IRF-1 than either IRF-3 or IRF-7 which has significance for evasion of basal anti-viral immunity and type III IFN induction in the intestinal epithelium. MDPI 2021-03-31 /pmc/articles/PMC8066714/ /pubmed/33807175 http://dx.doi.org/10.3390/v13040589 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Iaconis, Gennaro
Jackson, Ben
Childs, Kay
Boyce, Mark
Goodbourn, Stephen
Blake, Neil
Iturriza-Gomara, Miren
Seago, Julian
Rotavirus NSP1 Inhibits Type I and Type III Interferon Induction
title Rotavirus NSP1 Inhibits Type I and Type III Interferon Induction
title_full Rotavirus NSP1 Inhibits Type I and Type III Interferon Induction
title_fullStr Rotavirus NSP1 Inhibits Type I and Type III Interferon Induction
title_full_unstemmed Rotavirus NSP1 Inhibits Type I and Type III Interferon Induction
title_short Rotavirus NSP1 Inhibits Type I and Type III Interferon Induction
title_sort rotavirus nsp1 inhibits type i and type iii interferon induction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066714/
https://www.ncbi.nlm.nih.gov/pubmed/33807175
http://dx.doi.org/10.3390/v13040589
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