Binding of Lassa virus perturbs extracellular matrix-induced signal transduction via dystroglycan

Jillian M Rojek; Marie-Laurence Moraz; Christelle Pythoud; Sylvia Rothenberger; F. Gisou Van der Goot; Kevin P Campbell; Stefan Kunz

doi:10.1111/j.1462-5822.2012.01784.x

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Binding of Lassa virus perturbs extracellular matrix-induced signal transduction via dystroglycan

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Binding of Lassa virus perturbs extracellular matrix-induced signal transduction via dystroglycan

Jillian M Rojek, Marie-Laurence Moraz, Christelle Pythoud, Sylvia Rothenberger, F. Gisou Van der Goot, Kevin P Campbell and Stefan Kunz

Cellular microbiology, Vol.14(7), pp.1122-1134

07/2012

DOI: 10.1111/j.1462-5822.2012.01784.x

PMCID: PMC3869547

PMID: 22405130

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Abstract

The arenavirus Lassa virus (LASV) causes a severe haemorrhagic fever with high mortality in man. The cellular receptor for LASV is dystroglycan (DG). DG is a ubiquitous receptor for extracellular matrix (ECM) proteins, which cooperates with β1 integrins to control cell–matrix interactions. Here, we investigated whether LASV binding to DG triggers signal transduction, mimicking the natural ligands. Engagement of DG by LASV resulted in the recruitment of the adaptor protein Grb2 and the protein kinase MEK1 by the cytoplasmic domain of DG without activating the MEK/ERK pathway, indicating assembly of an inactive signalling complex. LASV binding to cells however affected the activation of the MEK/ERK pathway via α6β1 integrins. The virus-induced perturbation of α6β1 integrin signalling critically depended on high-affinity LASV binding to DG and DG’s cytoplasmic domain, indicating that LASV–receptor binding perturbed signalling cross-talk between DG and β1 integrins.

Details

Title: Subtitle: Binding of Lassa virus perturbs extracellular matrix-induced signal transduction via dystroglycan
Creators: Jillian M Rojek - Department of Immunology and Microbial Science, The Scripps Research Institute La Jolla, CA 92037, USA
Marie-Laurence Moraz - Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland
Christelle Pythoud - Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland
Sylvia Rothenberger - Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland
F. Gisou Van der Goot - Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Faculty of Life Sciences, Lausanne, Switzerland
Kevin P Campbell - Howard Hughes Medical Institute, Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, Department of Molecular Physiology and Biophysics, Department of Neurology, and Department of Internal Medicine, Roy J and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA
Stefan Kunz - Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland
Resource Type: Journal article
Publication Details: Cellular microbiology, Vol.14(7), pp.1122-1134
DOI: 10.1111/j.1462-5822.2012.01784.x
PMID: 22405130
PMCID: PMC3869547
NLM abbreviation: Cell Microbiol
ISSN: 1462-5814
eISSN: 1462-5822
Grant note: || HHMI_ / Howard Hughes Medical Institute :
Language: English
Date published: 07/2012
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984020846302771

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