Journal article
Old World Arenavirus Infection Interferes with the Expression of Functional α-Dystroglycan in the Host Cell
Molecular biology of the cell, Vol.18(11), pp.4493-4507
11/2007
DOI: 10.1091/mbc.e07-04-0374
PMCID: PMC2043543
PMID: 17761532
Abstract
α-Dystroglycan (α-DG) is an important cellular receptor for extracellular matrix (ECM) proteins as well as the Old World arenaviruses lymphocytic choriomeningitis virus (LCMV) and the human pathogenic Lassa fever virus (LFV). Specific O-glycosylation of α-DG is critical for its function as receptor for ECM proteins and arenaviruses. Here, we investigated the impact of arenavirus infection on α-DG expression. Infection with an immunosuppressive LCMV isolate caused a marked reduction in expression of functional α-DG without affecting biosynthesis of DG core protein or global cell surface glycoprotein expression. The effect was caused by the viral glycoprotein (GP), and it critically depended on α-DG binding affinity and GP maturation. An equivalent effect was observed with LFVGP. Viral GP was found to associate with a complex between DG and the glycosyltransferase LARGE in the Golgi. Overexpression of LARGE restored functional α-DG expression in infected cells. We provide evidence that virus-induced down-modulation of functional α-DG perturbs DG-mediated assembly of laminin at the cell surface, affecting normal cell–matrix interactions.
Details
- Title: Subtitle
- Old World Arenavirus Infection Interferes with the Expression of Functional α-Dystroglycan in the Host Cell
- Creators
- Jillian M Rojek - Viral Immunobiology Laboratory, Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA 92037; andKevin P Campbell - Departments of Molecular Physiology and Biophysics, Neurology, and Internal Medicine, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, IA 52242Michael B.A Oldstone - Viral Immunobiology Laboratory, Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA 92037; andStefan Kunz - Viral Immunobiology Laboratory, Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA 92037; and
- Contributors
- Jean Schwarzbauer (Editor)
- Resource Type
- Journal article
- Publication Details
- Molecular biology of the cell, Vol.18(11), pp.4493-4507
- DOI
- 10.1091/mbc.e07-04-0374
- PMID
- 17761532
- PMCID
- PMC2043543
- NLM abbreviation
- Mol Biol Cell
- ISSN
- 1059-1524
- eISSN
- 1939-4586
- Publisher
- American Society for Cell Biology
- Language
- English
- Date published
- 11/2007
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984020629302771
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