Cell entry of Lassa virus induces tyrosine phosphorylation of dystroglycan

Marie-Laurence Moraz; Christelle Pythoud; Rolf Turk; Sylvia Rothenberger; Antonella Pasquato; Kevin P Campbell; Stefan Kunz

doi:10.1111/cmi.12078

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Cell entry of Lassa virus induces tyrosine phosphorylation of dystroglycan

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Cell entry of Lassa virus induces tyrosine phosphorylation of dystroglycan

Marie-Laurence Moraz, Christelle Pythoud, Rolf Turk, Sylvia Rothenberger, Antonella Pasquato, Kevin P Campbell and Stefan Kunz

Cellular microbiology, Vol.15(5), pp.689-700

05/2013

DOI: 10.1111/cmi.12078

PMCID: PMC3805106

PMID: 23279385

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Abstract

The extracellular matrix (ECM) receptor dystroglycan (DG) serves as a cellular receptor for the highly pathogenic arenavirus Lassa virus (LASV) that causes a hemorrhagic fever with high mortality in man. In the host cell, DG provides a molecular link between the ECM and the actin cytoskeleton via the adapter proteins utrophin or dystrophin. Here we investigated post-translational modifications of DG in the context of LASV cell entry. Using the tyrosine kinase inhibitor genistein, we found that tyrosine kinases are required for efficient internalization of virus particles, but not virus-receptor binding. Engagement of cellular DG by LASV envelope glycoprotein (LASV GP) in human epithelial cells induced tyrosine phosphorylation of the cytoplasmic domain of DG. LASV GP binding to DG further resulted in dissociation of the adapter protein utrophin from virus-bound DG. This virus-induced dissociation of utrophin was affected by genistein treatment, suggesting a role of receptor tyrosine phosphorylation in the process.

Details

Title: Subtitle: Cell entry of Lassa virus induces tyrosine phosphorylation of dystroglycan
Creators: Marie-Laurence Moraz - Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
Christelle Pythoud - Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
Rolf Turk - 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, Iowa 52242, USA
Sylvia Rothenberger - Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
Antonella Pasquato - Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
Kevin P Campbell - University of Iowa, Molecular Physiology and Biophysics
Stefan Kunz - Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
Resource Type: Journal article
Publication Details: Cellular microbiology, Vol.15(5), pp.689-700
DOI: 10.1111/cmi.12078
PMID: 23279385
PMCID: PMC3805106
NLM abbreviation: Cell Microbiol
ISSN: 1462-5814
eISSN: 1462-5822
Publisher: Wiley
Grant note: || HHMI_ / Howard Hughes Medical Institute :
Language: English
Date published: 05/2013
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984031899402771

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