Posttranslational Modification of α-Dystroglycan, the Cellular Receptor for Arenaviruses, by the Glycosyltransferase LARGE Is Critical for Virus Binding

Stefan Kunz; Jillian M Rojek; Motoi Kanagawa; Christina F Spiropoulou; Rita Barresi; Kevin P Campbell; Michael B. A Oldstone

doi:10.1128/JVI.79.22.14282-14296.2005

Back

Posttranslational Modification of α-Dystroglycan, the Cellular Receptor for Arenaviruses, by the Glycosyltransferase LARGE Is Critical for Virus Binding

Journal article

Open access

Peer reviewed

Posttranslational Modification of α-Dystroglycan, the Cellular Receptor for Arenaviruses, by the Glycosyltransferase LARGE Is Critical for Virus Binding

Stefan Kunz, Jillian M Rojek, Motoi Kanagawa, Christina F Spiropoulou, Rita Barresi, Kevin P Campbell and Michael B. A Oldstone

Journal of virology, Vol.79(22), pp.14282-14296

11/2005

DOI: 10.1128/JVI.79.22.14282-14296.2005

PMCID: PMC1280193

PMID: 16254363

Files and links (1)

url

https://doi.org/10.1128/JVI.79.22.14282-14296.2005View

Published (Version of record) Open Access

Abstract

The receptor for lymphocytic choriomeningitis virus (LCMV), the human pathogenic Lassa fever virus (LFV), and clade C New World arenaviruses is α-dystroglycan (α-DG), a cell surface receptor for proteins of the extracellular matrix (ECM). Specific posttranslational modification of α-DG by the glycosyltransferase LARGE is critical for its function as an ECM receptor. In the present study, we show that LARGE-dependent modification is also crucial for α-DG's function as a cellular receptor for arenaviruses. Virus binding involves the mucin-type domain of α-DG and depends on modification by LARGE. A crucial role of the LARGE-dependent glycosylation of α-DG for virus binding is found for several isolates of LCMV, LFV, and the arenaviruses Mobala and Oliveros. Since the posttranslational modification by LARGE is crucial for α-DG recognition by both arenaviruses and the host-derived ligand laminin, it also influences competition between virus and laminin for α-DG. Hence, LARGE-dependent glycosylation of α-DG has important implications for the virus-host cell interaction and the pathogenesis of LFV in humans.

Virus-Cell Interactions

Details

Title: Subtitle: Posttranslational Modification of α-Dystroglycan, the Cellular Receptor for Arenaviruses, by the Glycosyltransferase LARGE Is Critical for Virus Binding
Creators: Stefan Kunz - Departments of Neuropharmacology
Jillian M Rojek - Departments of Neuropharmacology
Motoi Kanagawa - Departments of Neuropharmacology
Christina F Spiropoulou - Departments of Neuropharmacology
Rita Barresi - Departments of Neuropharmacology
Kevin P Campbell - Departments of Neuropharmacology
Michael B. A Oldstone - Departments of Neuropharmacology
Resource Type: Journal article
Publication Details: Journal of virology, Vol.79(22), pp.14282-14296
DOI: 10.1128/JVI.79.22.14282-14296.2005
PMID: 16254363
PMCID: PMC1280193
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: American Society for Microbiology
Language: English
Date published: 11/2005
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984020777702771

Metrics

15 Record Views

127 Times Cited - Web of Science