Old World arenavirus infection interferes with the expression of functional alpha-dystroglycan in the host cell.

Details

Serval ID
serval:BIB_45C80C80D68F
Type
Article: article from journal or magazin.
Collection
Publications
Title
Old World arenavirus infection interferes with the expression of functional alpha-dystroglycan in the host cell.
Journal
Molecular Biology of the Cell
Author(s)
Rojek J.M., Campbell K.P., Oldstone M.B., Kunz S.
ISSN
1059-1524 (Print)
ISSN-L
1059-1524
Publication state
Published
Issued date
2007
Volume
18
Number
11
Pages
4493-4507
Language
english
Abstract
alpha-Dystroglycan (alpha-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 alpha-DG is critical for its function as receptor for ECM proteins and arenaviruses. Here, we investigated the impact of arenavirus infection on alpha-DG expression. Infection with an immunosuppressive LCMV isolate caused a marked reduction in expression of functional alpha-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 alpha-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 alpha-DG expression in infected cells. We provide evidence that virus-induced down-modulation of functional alpha-DG perturbs DG-mediated assembly of laminin at the cell surface, affecting normal cell-matrix interactions.
Keywords
Animals, Arenaviruses, Old World/physiology, Cell Line, Cercopithecus aethiops, Dystroglycans/metabolism, Gene Expression Regulation, Glycosylation, Glycosyltransferases/genetics, Glycosyltransferases/metabolism, Humans, Laminin/metabolism, Mice, Protein Binding, Transcription, Genetic/genetics, Viral Proteins/metabolism
Pubmed
Web of science
Create date
17/04/2013 12:56
Last modification date
03/03/2018 16:46
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