title: Measles virus modulates dendritic cell/T-cell communication at the level of plexinA1/neuropilin-1 recruitment and activity.
abstract: Measles virus (MV)-infected DC fail to promote T-cell expansion, and this could explain important aspects of measles immunosuppression. The efficiency of the immune synapse (IS) is determined by the formation of stable, stimulatory conjugates involving a spatially and timely controlled architecture. PlexinA1 (plexA1) and its co-receptor neuropilin (NP-1) have been implicated in IS efficiency, while their repulsive ligand, SEMA3A, likely acts in terminating T-cell activation. Conjugates involving MV-infected DC and T cells are unstable and not stimulatory, and thus we addressed the potential role of plexA1/NP-1 and semaphorins (SEMAs) in this system. MV does not grossly affect expression levels of plexA1/NP-1 on T cells or DC, yet prevents their recruitment towards stimulatory interfaces. Moreover, MV infection promoted early release of SEMA3A from DC, which caused loss of actin based protrusions on T cells as did the plexA4 ligand SEMA6A. SEMA3A/6A differentially modulated chemokinetic migration of T cells and conjugation with allogeneic DC. Thus, MV targets SEMA receptor function both at the level of IS recruitment, and by promoting a timely inappropriate release of their repulsive ligand, SEMA3A. To the best of our knowledge, this is the first example of viral targeting of SEMA receptor function in the IS.
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, Wuerzburg, Germany.
authors.forename: Hieu
authors.initials: H
authors.lastname: Tran-Van
authors.forename: Elita
authors.initials: E
authors.lastname: Avota
authors.forename: Charlene
authors.initials: C
authors.lastname: Börtlein
authors.forename: Nora
authors.initials: N
authors.lastname: Mueller
authors.forename: Sibylle
authors.initials: S
authors.lastname: Schneider-Schaulies
mesh_terms: D002450:Cell Communication / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D006801:Humans; D054992:Immunological Synapses / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D008459:Measles virus / Q000276:immunology*; D009419:Nerve Tissue Proteins / Q000276:immunology*; D039942:Neuropilin-1 / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology*; D039961:Semaphorins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology
chemical_list: D009419:Nerve Tissue Proteins; C492116:PLXNA1 protein, human; D011956:Receptors, Cell Surface; D039961:Semaphorins; D039942:Neuropilin-1