title: Severe impairment of dendritic cell allostimulatory activity by Sendai virus vectors is overcome by matrix protein gene deletion.
abstract: Delivery of Ags to dendritic cells (DCs) plays a pivotal role in the induction of efficient immune responses ranging from immunity to tolerance. The observation that certain viral pathogens are able to infect DCs has led to a concept in which applications of recombinant viruses are used for Ag delivery with the potential benefit of inducing potent Ag-specific T cell responses directed against multiple epitopes. As a prerequisite for such an application, the infection of DCs by recombinant viruses should not interfere with their stimulatory capacity. In this context, we could show that an emerging negative-strand RNA viral vector system based on the Sendai virus (SeV) is able to efficiently infect monocyte-derived human DCs (moDCs). However, after infection with SeV wild type, both the response of DCs to bacterial LPS as a powerful mediator of DC maturation and the allostimulatory activity were severely impaired. Interestingly, using various recombinant SeV vectors that were devoid of single viral genes, we were able to identify the SeV matrix (M) protein as a key component in moDC functional impairment after viral infection. Consequently, use of M-deficient SeV vectors preserved the allostimulatory activity in infected moDCs despite an efficient expression of all other virally encoded genes, thereby identifying M-deficient vectors as a highly potent tool for the genetic manipulation of DCs.
authors.affiliation: Department of Internal Medicine I, University Clinic Tübingen, Tübingen, Germany.
authors.forename: Sorin
authors.initials: S
authors.lastname: Armeanu
authors.forename: Michael
authors.initials: M
authors.lastname: Bitzer
authors.forename: Irina
authors.initials: I
authors.lastname: Smirnow
authors.forename: Sascha
authors.initials: S
authors.lastname: Bossow
authors.forename: Silke
authors.initials: S
authors.lastname: Appel
authors.forename: Guy
authors.initials: G
authors.lastname: Ungerechts
authors.forename: Christian
authors.initials: C
authors.lastname: Bernloehr
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Neubert
authors.forename: Ulrich M
authors.initials: UM
authors.lastname: Lauer
authors.forename: Peter
authors.initials: P
authors.lastname: Brossart
mesh_terms: D017209:Apoptosis / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D017353:Gene Deletion; D005822:Genetic Vectors / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D008070:Lipopolysaccharides / Q000276:immunology; D029082:Sendai virus / Q000235:genetics / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D014771:Virion / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D014763:Viral Matrix Proteins