title: Alpha-dystroglycan can mediate arenavirus infection in the absence of beta-dystroglycan.
abstract: Dystroglycan (DG) is a highly versatile cell surface molecule that provides a molecular link between the extracellular matrix (ECM) and the actin-based cytoskeleton. Encoded by a single gene, DG is posttranslationally processed to form alpha-DG, a peripheral protein identified as the cellular receptor for lymphocytic choriomeningitis virus (LCMV) and Lassa fever virus (LFV), and the membrane-spanning subunit beta-DG. The link of beta-DG to the actin-based cytoskeleton and its association with the cellular signal transduction network suggest that it may function as an essential cofactor for the activity of alpha-DG as a virus receptor. To address this issue, we constructed a deletion mutant lacking the cytoplasmic domain of beta-DG and a C-terminal fusion between alpha-DG and the transmembrane domain of PDGF receptor. Both mutants were functional as virus receptors, indicating that beta-DG does not act as a cofactor with alpha-DG for arenavirus binding and entry. These observations are in agreement with the fact that LCMV infection is independent from the structural integrity of the actin-based cytoskeleton and suggest that alpha-DG functions primarily in the attachment of arenaviruses to the cell surface.
authors.affiliation: The Scripps Research Institute, Department of Neuropharmacology, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA. stefanku@scripps.edu
authors.forename: Stefan
authors.initials: S
authors.lastname: Kunz
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Campbell
authors.forename: Michael B A
authors.initials: MB
authors.lastname: Oldstone
mesh_terms: D000818:Animals; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000502:physiology*; D049030:Dystroglycans; D008216:Lymphocytic Choriomeningitis / Q000209:etiology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D011991:Receptors, Virus / Q000502:physiology*
chemical_list: D003598:Cytoskeletal Proteins; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D049030:Dystroglycans