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Open AccessArticle

The Microtubule-Associated Innate Immune Sensor GEF-H1 Does Not Influence Mouse Norovirus Replication in Murine Macrophages

1
Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3010, Australia
2
School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW 2052, Australia
*
Author to whom correspondence should be addressed.
Present address: Department of Microbiology, School of Biomedical Sciences, Monash University, Melbourne, VIC 3010, Australia.
Viruses 2019, 11(1), 47; https://doi.org/10.3390/v11010047
Received: 22 November 2018 / Revised: 7 January 2019 / Accepted: 8 January 2019 / Published: 10 January 2019
(This article belongs to the Special Issue Noroviruses)
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. View Full-Text
Keywords: mouse norovirus; innate immunity; microtubules; GEF-H1 mouse norovirus; innate immunity; microtubules; GEF-H1
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Fritzlar, S.; White, P.A.; Mackenzie, J.M. The Microtubule-Associated Innate Immune Sensor GEF-H1 Does Not Influence Mouse Norovirus Replication in Murine Macrophages. Viruses 2019, 11, 47.

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