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The Microtubule-Associated Innate Immune Sensor GEF-H1 Does Not Influence Mouse Norovirus Replication in Murine Macrophages
Norovirus is an acute infection of the gastrointestinal tract causing rapid induction of vomiting and diarrhoea. The infection is sensed and controlled by the innate immune system, particularly by the RNA helicase MDA-5 and type I and III interferons (IFNs). We have observed that intracellular repli...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356845/ https://www.ncbi.nlm.nih.gov/pubmed/30634661 http://dx.doi.org/10.3390/v11010047 |
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author | Fritzlar, Svenja White, Peter A. Mackenzie, Jason M. |
author_facet | Fritzlar, Svenja White, Peter A. Mackenzie, Jason M. |
author_sort | Fritzlar, Svenja |
collection | PubMed |
description | Norovirus is an acute infection of the gastrointestinal tract causing rapid induction of vomiting and diarrhoea. The infection is sensed and controlled by the innate immune system, particularly by the RNA helicase MDA-5 and type I and III interferons (IFNs). We have observed that intracellular replication of murine norovirus (MNV) occurs in membranous clusters proximal to the microtubule organising centre, a localisation dependent on intact microtubules. Recently, it was shown that the host protein guanine nucleotide exchange factor-H1 (GEF-H1) is a microtubule-associated innate immune sensor that activates interferon Regulatory Factor 3 to induce the production of type I IFNs. Thus, we interrogated the potential role of GEF-H1 in controlling MNV infections. We observed that GEF-H1 was recruited to the MNV replication complex; however RNAi-mediated suppression of GEF-H1 did not outwardly affect replication. We furthered our studies to investigate the impact of GEF-H1 on MNV innate detection and observed that GEF-H1 did not contribute to type I IFN induction during MNV infection or influenza virus infection but did result in a small reduction of interferon–β (IFNβ) during West Nile virus infection. Intriguingly, we discovered an interaction of GEF-H1 with the viral MNV non-structural protein 3 (NS3), an interaction that altered the location of GEF-H1 within the cell and prevented the formation of GEF-H1-induced microtubule fibres. Thus, our results indicate that GEF-H1 does not contribute significantly to the innate immune sensing of MNV, although its function may be modulated via interaction with the viral NS3 protein. |
format | Online Article Text |
id | pubmed-6356845 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63568452019-02-05 The Microtubule-Associated Innate Immune Sensor GEF-H1 Does Not Influence Mouse Norovirus Replication in Murine Macrophages Fritzlar, Svenja White, Peter A. Mackenzie, Jason M. Viruses Article Norovirus is an acute infection of the gastrointestinal tract causing rapid induction of vomiting and diarrhoea. The infection is sensed and controlled by the innate immune system, particularly by the RNA helicase MDA-5 and type I and III interferons (IFNs). We have observed that intracellular replication of murine norovirus (MNV) occurs in membranous clusters proximal to the microtubule organising centre, a localisation dependent on intact microtubules. Recently, it was shown that the host protein guanine nucleotide exchange factor-H1 (GEF-H1) is a microtubule-associated innate immune sensor that activates interferon Regulatory Factor 3 to induce the production of type I IFNs. Thus, we interrogated the potential role of GEF-H1 in controlling MNV infections. We observed that GEF-H1 was recruited to the MNV replication complex; however RNAi-mediated suppression of GEF-H1 did not outwardly affect replication. We furthered our studies to investigate the impact of GEF-H1 on MNV innate detection and observed that GEF-H1 did not contribute to type I IFN induction during MNV infection or influenza virus infection but did result in a small reduction of interferon–β (IFNβ) during West Nile virus infection. Intriguingly, we discovered an interaction of GEF-H1 with the viral MNV non-structural protein 3 (NS3), an interaction that altered the location of GEF-H1 within the cell and prevented the formation of GEF-H1-induced microtubule fibres. Thus, our results indicate that GEF-H1 does not contribute significantly to the innate immune sensing of MNV, although its function may be modulated via interaction with the viral NS3 protein. MDPI 2019-01-10 /pmc/articles/PMC6356845/ /pubmed/30634661 http://dx.doi.org/10.3390/v11010047 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Fritzlar, Svenja White, Peter A. Mackenzie, Jason M. The Microtubule-Associated Innate Immune Sensor GEF-H1 Does Not Influence Mouse Norovirus Replication in Murine Macrophages |
title | The Microtubule-Associated Innate Immune Sensor GEF-H1 Does Not Influence Mouse Norovirus Replication in Murine Macrophages |
title_full | The Microtubule-Associated Innate Immune Sensor GEF-H1 Does Not Influence Mouse Norovirus Replication in Murine Macrophages |
title_fullStr | The Microtubule-Associated Innate Immune Sensor GEF-H1 Does Not Influence Mouse Norovirus Replication in Murine Macrophages |
title_full_unstemmed | The Microtubule-Associated Innate Immune Sensor GEF-H1 Does Not Influence Mouse Norovirus Replication in Murine Macrophages |
title_short | The Microtubule-Associated Innate Immune Sensor GEF-H1 Does Not Influence Mouse Norovirus Replication in Murine Macrophages |
title_sort | microtubule-associated innate immune sensor gef-h1 does not influence mouse norovirus replication in murine macrophages |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356845/ https://www.ncbi.nlm.nih.gov/pubmed/30634661 http://dx.doi.org/10.3390/v11010047 |
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