Journal article
Molecular analysis of the interaction of LCMV with its cellular receptor α-dystroglycan
The Journal of cell biology, Vol.155(2), pp.301-310
10/15/2001
DOI: 10.1083/jcb.200104103
PMCID: PMC2198839
PMID: 11604425
Abstract
α-Dystroglycan (DG) has been identified as the cellular receptor for lymphocytic choriomeningitis virus (LCMV) and Lassa fever virus (LFV). This subunit of DG is a highly versatile cell surface molecule that provides a molecular link between the extracellular matrix (ECM) and a β-DG transmembrane component, which interacts with the actin-based cytoskeleton. In addition, DG exhibits a complex pattern of interaction with a wide variety of ECM and cellular proteins. In the present study, we characterized the binding of LCMV to α-DG and addressed the role of α-DG–associated host-derived proteins in virus infection. We found that the COOH-terminal region of α-DG's first globular domain and the NH2-terminal region of the mucin-related structures of α-DG together form the binding site for LCMV. The virus–α-DG binding unlike ECM α-DG interactions was not dependent on divalent cations. Despite such differences in binding, LCMV and laminin-1 use, in part, an overlapping binding site on α-DG, and the ability of an LCMV isolate to compete with laminin-1 for receptor binding is determined by its binding affinity to α-DG. This competition of the virus with ECM molecules for receptor binding likely explains the recently found correlation between the affinity of LCMV binding to α-DG, tissue tropism, and pathological potential. LCMV strains and variants with high binding affinity to α-DG but not low affinity binders are able to infect CD11c+ dendritic cells, which express α-DG at their surface. Infection followed by dysfunction of these antigen-presenting cells contributes to immunosuppression and persistent viral infection in vivo.
Details
- Title: Subtitle
- Molecular analysis of the interaction of LCMV with its cellular receptor α-dystroglycan
- Creators
- Stefan Kunz - The Scripps Research Institute, Division of Virology, Department of Neuropharmacology, La Jolla, CA 92037Noemí Sevilla - The Scripps Research Institute, Division of Virology, Department of Neuropharmacology, La Jolla, CA 92037Dorian B McGavern - The Scripps Research Institute, Division of Virology, Department of Neuropharmacology, La Jolla, CA 92037Kevin P Campbell - Howard Hughes Medical Institute, University of Iowa College of Medicine, Department of Physiology and Biophysics, Neurology, Iowa City, IA 52242Michael B.A Oldstone - The Scripps Research Institute, Division of Virology, Department of Neuropharmacology, La Jolla, CA 92037
- Resource Type
- Journal article
- Publication Details
- The Journal of cell biology, Vol.155(2), pp.301-310
- DOI
- 10.1083/jcb.200104103
- PMID
- 11604425
- PMCID
- PMC2198839
- ISSN
- 0021-9525
- eISSN
- 1540-8140
- Language
- English
- Date published
- 10/15/2001
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984020992002771
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