title: O Mannosylation of alpha-dystroglycan is essential for lymphocytic choriomeningitis virus receptor function.
abstract: Alpha-dystroglycan (alpha-DG) was identified as a common receptor for lymphocytic choriomeningitis virus (LCMV) and several other arenaviruses including the human pathogenic Lassa fever virus. Initial work postulated that interactions between arenavirus glycoproteins and alpha-DG are based on protein-protein interactions. We found, however, that susceptibility toward LCMV infection differed in various cell lines despite them expressing comparable levels of DG, suggesting that posttranslational modifications of alpha-DG would be involved in viral receptor function. Here, we demonstrate that glycosylation of alpha-DG, and in particular, O mannosylation, which is a rare type of O-linked glycosylation in mammals, is essential for LCMV receptor function. Cells that are defective in components of the O-mannosylation pathway showed strikingly reduced LCMV infectibility. As defective O mannosylation is associated with severe clinical symptoms in mammals such as congenital muscular dystrophies, it is likely that LCMV and potentially other arenaviruses may have selected this conserved and crucial posttranslational modification as the primary target structure for cell entry and infection.
authors.affiliation: Institute for Microbiology, ETH Zurich, 8093 Zürich, Switzerland.
authors.forename: Mauro
authors.initials: M
authors.lastname: Imperiali
authors.forename: Claudio
authors.initials: C
authors.lastname: Thoma
authors.forename: Ernesto
authors.initials: E
authors.lastname: Pavoni
authors.forename: Andrea
authors.initials: A
authors.lastname: Brancaccio
authors.forename: Nico
authors.initials: N
authors.lastname: Callewaert
authors.forename: Annette
authors.initials: A
authors.lastname: Oxenius
mesh_terms: D000818:Animals; D001117:Arenaviridae Infections; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D004285:Dogs; D049030:Dystroglycans / Q000378:metabolism*; D005347:Fibroblasts / Q000502:physiology / Q000821:virology; D005434:Flow Cytometry; D006031:Glycosylation; D006801:Humans; D019169:Jurkat Cells; D007739:L Cells; D008216:Lymphocytic Choriomeningitis; D008217:Lymphocytic choriomeningitis virus / Q000472:pathogenicity / Q000502:physiology*; D008358:Mannose / Q000378:metabolism*; D051379:Mice; D011991:Receptors, Virus / Q000502:physiology*
chemical_list: D011991:Receptors, Virus; D049030:Dystroglycans; D008358:Mannose