title: Binding of Lassa virus perturbs extracellular matrix-induced signal transduction via dystroglycan.
abstract: The arenavirus Lassa virus (LASV) causes a severe haemorrhagic fever with high mortality in man. The cellular receptor for LASV is dystroglycan (DG). DG is a ubiquitous receptor for extracellular matrix (ECM) proteins, which cooperates with β1 integrins to control cell-matrix interactions. Here, we investigated whether LASV binding to DG triggers signal transduction, mimicking the natural ligands. Engagement of DG by LASV resulted in the recruitment of the adaptor protein Grb2 and the protein kinase MEK1 by the cytoplasmic domain of DG without activating the MEK/ERK pathway, indicating assembly of an inactive signalling complex. LASV binding to cells however affected the activation of the MEK/ERK pathway via α6β1 integrins. The virus-induced perturbation of α6β1 integrin signalling critically depended on high-affinity LASV binding to DG and DG's cytoplasmic domain, indicating that LASV-receptor binding perturbed signalling cross-talk between DG and β1 integrins.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Jillian M
authors.initials: JM
authors.lastname: Rojek
authors.forename: Marie-Laurence
authors.initials: ML
authors.lastname: Moraz
authors.forename: Christelle
authors.initials: C
authors.lastname: Pythoud
authors.forename: Sylvia
authors.initials: S
authors.lastname: Rothenberger
authors.forename: F Gisou
authors.initials: FG
authors.lastname: Van der Goot
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Campbell
authors.forename: Stefan
authors.initials: S
authors.lastname: Kunz
mesh_terms: D002460:Cell Line; D049030:Dystroglycans / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D007836:Lassa virus / Q000472:pathogenicity* / Q000502:physiology; D008954:Models, Biological; D011991:Receptors, Virus / Q000378:metabolism*; D015398:Signal Transduction; D053585:Virus Attachment
chemical_list: D019012:Integrin beta1; D011991:Receptors, Virus; D049030:Dystroglycans