Posttranslational modification of alpha-dystroglycan, the cellular receptor for arenaviruses, by the glycosyltransferase LARGE is critical for virus binding.
Details
Serval ID
serval:BIB_E34C3C5FE6D1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Posttranslational modification of alpha-dystroglycan, the cellular receptor for arenaviruses, by the glycosyltransferase LARGE is critical for virus binding.
Journal
Journal of Virology
ISSN
0022-538X (Print)
ISSN-L
0022-538X
Publication state
Published
Issued date
2005
Volume
79
Number
22
Pages
14282-14296
Language
english
Abstract
The receptor for lymphocytic choriomeningitis virus (LCMV), the human pathogenic Lassa fever virus (LFV), and clade C New World arenaviruses is alpha-dystroglycan (alpha-DG), a cell surface receptor for proteins of the extracellular matrix (ECM). Specific posttranslational modification of alpha-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 alpha-DG's function as a cellular receptor for arenaviruses. Virus binding involves the mucin-type domain of alpha-DG and depends on modification by LARGE. A crucial role of the LARGE-dependent glycosylation of alpha-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 alpha-DG recognition by both arenaviruses and the host-derived ligand laminin, it also influences competition between virus and laminin for alpha-DG. Hence, LARGE-dependent glycosylation of alpha-DG has important implications for the virus-host cell interaction and the pathogenesis of LFV in humans.
Keywords
Animals, Arenaviridae/metabolism, Arenaviridae/physiology, Base Sequence, Crosses, Genetic, DNA Primers, DNA-Directed RNA Polymerases/metabolism, Dystroglycans/metabolism, Female, Kinetics, Male, Mice, Mice, Inbred C57BL, N-Acetylglucosaminyltransferases/metabolism, Protein Processing, Post-Translational, Viral Proteins/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
17/04/2013 11:56
Last modification date
20/08/2019 16:07