title: Characterization of the interaction of lassa fever virus with its cellular receptor alpha-dystroglycan.
abstract: The cellular receptor for the Old World arenaviruses Lassa fever virus (LFV) and lymphocytic choriomeningitis virus (LCMV) has recently been identified as alpha-dystroglycan (alpha-DG), a cell surface receptor that provides a molecular link between the extracellular matrix and the actin-based cytoskeleton. In the present study, we show that LFV binds to alpha-DG with high affinity in the low-nanomolar range. Recombinant vesicular stomatitis virus pseudotyped with LFV glycoprotein (GP) adopted the receptor binding characteristics of LFV and depended on alpha-DG for infection of cells. Mapping of the binding site of LFV on alpha-DG revealed that LFV binding required the same domains of alpha-DG that are involved in the binding of LCMV. Further, LFV was found to efficiently compete with laminin alpha1 and alpha2 chains for alpha-DG binding. Together with our previous studies on receptor binding of the prototypic immunosuppressive LCMV isolate LCMV clone 13, these findings indicate a high degree of conservation in the receptor binding characteristics between the highly human-pathogenic LFV and murine-immunosuppressive LCMV isolates.
authors.affiliation: Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA. stefanku@scripps.edu
authors.forename: Stefan
authors.initials: S
authors.lastname: Kunz
authors.forename: Jillian M
authors.initials: JM
authors.lastname: Rojek
authors.forename: Mar
authors.initials: M
authors.lastname: Perez
authors.forename: Christina F
authors.initials: CF
authors.lastname: Spiropoulou
authors.forename: Michael B A
authors.initials: MB
authors.lastname: Oldstone
mesh_terms: D001665:Binding Sites; D049030:Dystroglycans / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007835:Lassa Fever / Q000821:virology*; D007836:Lassa virus / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D011991:Receptors, Virus; D049030:Dystroglycans