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Molecular analysis of the interaction of lcmv with its cellular receptor alpha-dystroglycan

Academic Article
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Overview

authors

  • Kunz, S.
  • Sevilla, N.
  • McGavern, Dorian
  • Campbell, K. P.
  • Oldstone, Michael

publication date

  • October 2001

journal

  • Journal of Cell Biology  Journal

abstract

  • alpha-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 beta-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 alpha-DG and addressed the role of alpha-DG-associated host-derived proteins in virus infection. We found that the COOH-terminal region of alpha-DG's first globular domain and the NH2-terminal region of the mucin-related structures of alpha-DG together form the binding site for LCMV. The virus-alpha-DG binding unlike ECM alpha-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 alpha-DG, and the ability of an LCMV isolate to compete with laminin-1 for receptor binding is determined by its binding affinity to alpha-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 alpha-DG, tissue tropism, and pathological potential. LCMV strains and variants with high binding affinity to alpha-DG but not low affinity binders are able to infect CD11c+ dendritic cells, which express alpha-DG at their surface. Infection followed by dysfunction of these antigen-presenting cells contributes to immunosuppression and persistent viral infection in vivo.

subject areas

  • Animals
  • Arenaviridae Infections
  • Binding Sites
  • Binding, Competitive
  • Cells, Cultured
  • Cytoskeletal Proteins
  • Dystroglycans
  • Extracellular Matrix Proteins
  • Female
  • Laminin
  • Lymphocytic choriomeningitis virus
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred C57BL
  • Protein Structure, Tertiary
  • Spleen
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Research

keywords

  • binding site
  • extracellular matrix
  • lymphocytic choriomeningitis virus
  • pathogenesis
  • viral receptor
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Identity

PubMed Central ID

  • PMC2198839

International Standard Serial Number (ISSN)

  • 0021-9525

Digital Object Identifier (DOI)

  • 10.1083/jcb.200104103

PubMed ID

  • 11604425
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Additional Document Info

start page

  • 301

end page

  • 310

volume

  • 155

issue

  • 2

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