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The RNA binding protein La/SS-B promotes RIG-I-mediated type I and type III IFN responses following Sendai viral infection
La/SS-B (or La) is a 48 kDa RNA-binding protein and an autoantigen in autoimmune disorders such as systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SS). La involvement in regulating the type I interferon (IFN) response is controversial - acting through both positive and negative regulatory...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5673980/ https://www.ncbi.nlm.nih.gov/pubmed/29109527 http://dx.doi.org/10.1038/s41598-017-15197-9 |
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author | Mahony, Rebecca Broadbent, Lindsay Maier-Moore, Jacen S. Power, Ultan F. Jefferies, Caroline A. |
author_facet | Mahony, Rebecca Broadbent, Lindsay Maier-Moore, Jacen S. Power, Ultan F. Jefferies, Caroline A. |
author_sort | Mahony, Rebecca |
collection | PubMed |
description | La/SS-B (or La) is a 48 kDa RNA-binding protein and an autoantigen in autoimmune disorders such as systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SS). La involvement in regulating the type I interferon (IFN) response is controversial - acting through both positive and negative regulatory mechanisms; inhibiting the IFN response and enhancing viral growth, or directly inhibiting viral replication. We therefore sought to clarify how La regulates IFN production in response to viral infection. ShRNA knockdown of La in HEK 293 T cells increased Sendai virus infection efficiency, decreased IFN-β, IFN-λ1, and interferon-stimulated chemokine gene expression. In addition, knockdown attenuated CCL-5 and IFN-λ1 secretion. Thus, La has a positive role in enhancing type I and type III IFN production. Mechanistically, we show that La directly binds RIG-I and have mapped this interaction to the CARD domains of RIG-I and the N terminal domain of La. In addition, we showed that this interaction is induced following RIG-I activation and that overexpression of La enhances RIG-I-ligand binding. Together, our results demonstrate a novel role for La in mediating RIG-I-driven responses downstream of viral RNA detection, ultimately leading to enhanced type I and III IFN production and positive regulation of the anti-viral response. |
format | Online Article Text |
id | pubmed-5673980 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56739802017-11-15 The RNA binding protein La/SS-B promotes RIG-I-mediated type I and type III IFN responses following Sendai viral infection Mahony, Rebecca Broadbent, Lindsay Maier-Moore, Jacen S. Power, Ultan F. Jefferies, Caroline A. Sci Rep Article La/SS-B (or La) is a 48 kDa RNA-binding protein and an autoantigen in autoimmune disorders such as systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SS). La involvement in regulating the type I interferon (IFN) response is controversial - acting through both positive and negative regulatory mechanisms; inhibiting the IFN response and enhancing viral growth, or directly inhibiting viral replication. We therefore sought to clarify how La regulates IFN production in response to viral infection. ShRNA knockdown of La in HEK 293 T cells increased Sendai virus infection efficiency, decreased IFN-β, IFN-λ1, and interferon-stimulated chemokine gene expression. In addition, knockdown attenuated CCL-5 and IFN-λ1 secretion. Thus, La has a positive role in enhancing type I and type III IFN production. Mechanistically, we show that La directly binds RIG-I and have mapped this interaction to the CARD domains of RIG-I and the N terminal domain of La. In addition, we showed that this interaction is induced following RIG-I activation and that overexpression of La enhances RIG-I-ligand binding. Together, our results demonstrate a novel role for La in mediating RIG-I-driven responses downstream of viral RNA detection, ultimately leading to enhanced type I and III IFN production and positive regulation of the anti-viral response. Nature Publishing Group UK 2017-11-06 /pmc/articles/PMC5673980/ /pubmed/29109527 http://dx.doi.org/10.1038/s41598-017-15197-9 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Mahony, Rebecca Broadbent, Lindsay Maier-Moore, Jacen S. Power, Ultan F. Jefferies, Caroline A. The RNA binding protein La/SS-B promotes RIG-I-mediated type I and type III IFN responses following Sendai viral infection |
title | The RNA binding protein La/SS-B promotes RIG-I-mediated type I and type III IFN responses following Sendai viral infection |
title_full | The RNA binding protein La/SS-B promotes RIG-I-mediated type I and type III IFN responses following Sendai viral infection |
title_fullStr | The RNA binding protein La/SS-B promotes RIG-I-mediated type I and type III IFN responses following Sendai viral infection |
title_full_unstemmed | The RNA binding protein La/SS-B promotes RIG-I-mediated type I and type III IFN responses following Sendai viral infection |
title_short | The RNA binding protein La/SS-B promotes RIG-I-mediated type I and type III IFN responses following Sendai viral infection |
title_sort | rna binding protein la/ss-b promotes rig-i-mediated type i and type iii ifn responses following sendai viral infection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5673980/ https://www.ncbi.nlm.nih.gov/pubmed/29109527 http://dx.doi.org/10.1038/s41598-017-15197-9 |
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