title: Electron microscopy of an alpha-dystroglycan fragment containing receptor sites for lymphocytic choriomeningitis virus and laminin, and use of the receptoid body as a reagent to neutralize virus.
abstract: We report the electron microscopic structure of an alpha-dystroglycan (alpha-DG) fragment (DGEKFc4) that contains binding sites for lymphocytic choriomeningitis virus (LCMV) and the extracellular matrix (ECM) molecule laminin. In electron microscopic images, DGEKFc4 appears as dumbbell-shaped rods with a length of 7.5 +/- 0.5 nM and width of 3 +/- 0.3 nM. The C-terminal human Fc allows binding of anti-human Fc antibody resulting in formation of immune complexes that preserve alpha-DG binding to virus. Electron microscopy shows the antibody binding to near one end of the dumbbell-shaped rods. Because arenaviruses like LCMV or Lassa fever virus (LFV) generate poor neutralizing antibodies during natural infection or vaccination, we assayed whether the alpha-DG receptoid bodies generated could be used as an efficient antibody mimic. However, the receptor body formed by either alpha-DG fragment alone or complexed to antibody to human Fc failed to efficiently neutralize virus.
authors.affiliation: Viral-Immunobiology Laboratory, Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 91037, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kunz
authors.forename: Lesley
authors.initials: L
authors.lastname: Calder
authors.forename: Michael B A
authors.initials: MB
authors.lastname: Oldstone
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology / Q000648:ultrastructure*; D017931:DNA Primers / Q000235:genetics; D049030:Dystroglycans; D006801:Humans; D066298:In Vitro Techniques; D008217:Lymphocytic choriomeningitis virus / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology / Q000648:ultrastructure*; D008854:Microscopy, Electron; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000502:physiology / Q000648:ultrastructure*; D011817:Rabbits; D017474:Receptors, Laminin / Q000502:physiology; D011991:Receptors, Virus / Q000502:physiology
chemical_list: D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D017931:DNA Primers; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D017474:Receptors, Laminin; D011991:Receptors, Virus; D049030:Dystroglycans