JCB logo
Get More Out of Microscopy - Agilent iMIC 2000
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 15 October 2001. doi:10.1083/jcb.200104103
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kunz, S.
Right arrow Articles by Oldstone, M. B.A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kunz, S.
Right arrow Articles by Oldstone, M. B.A.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© The Rockefeller University Press, 0021-9525/2001/10/301 $5.00
The Journal of Cell Biology, Volume 155, Number 2, October 15, 2001 301-310

Article

 Molecular analysis of the interaction of LCMV with its cellular receptor {alpha}-dystroglycan

Stefan Kunz1, Noemí Sevilla1, Dorian B. McGavern1, Kevin P. Campbell2 and Michael B.A. Oldstone1

1 The Scripps Research Institute, Division of Virology, Department of Neuropharmacology, La Jolla, CA 92037
2 Howard Hughes Medical Institute, University of Iowa College of Medicine, Department of Physiology and Biophysics, Neurology, Iowa City, IA 52242

Address correspondence to Michael B.A. Oldstone, The Scripps Research Institute, Div. of Virology, Dept. of Neuropharmacology, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Tel.: (858) 784-8054. Fax: (858) 784-9981. E-mail: mbaobo{at}scripps.edu

{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 ß-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.

Key Words: lymphocytic choriomeningitis virus; viral receptor; binding site; extracellular matrix; pathogenesis


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents