title: Nonspreading Rift Valley Fever Virus Infection of Human Dendritic Cells Results in Downregulation of CD83 and Full Maturation of Bystander Cells.
abstract: Vaccines based on nonspreading Rift Valley fever virus (NSR) induce strong humoral and robust cellular immune responses with pronounced Th1 polarisation. The present work was aimed to gain insight into the molecular basis of NSR-mediated immunity. Recent studies have demonstrated that wild-type Rift Valley fever virus efficiently targets and replicates in dendritic cells (DCs). We found that NSR infection of cultured human DCs results in maturation of DCs, characterized by surface upregulation of CD40, CD80, CD86, MHC-I and MHC-II and secretion of the proinflammatory cytokines IFN-β, IL-6 and TNF. Interestingly, expression of the most prominent marker of DC maturation, CD83, was consistently downregulated at 24 hours post infection. Remarkably, NSR infection also completely abrogated CD83 upregulation by LPS. Downregulation of CD83 was not associated with reduced mRNA levels or impaired CD83 mRNA transport from the nucleus and could not be prevented by inhibition of the proteasome or endocytic degradation pathways, suggesting that suppression occurs at the translational level. In contrast to infected cells, bystander DCs displayed full maturation as evidenced by upregulation of CD83. Our results indicate that bystander DCs play an important role in NSR-mediated immunity.
authors.affiliation: Department of Virology, Central Veterinary Institute, part of Wageningen University and Research Centre, Lelystad, The Netherlands.|Department of Infectious Diseases and Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Nadia
authors.initials: N
authors.lastname: Oreshkova
authors.affiliation: Department of Virology, Central Veterinary Institute, part of Wageningen University and Research Centre, Lelystad, The Netherlands.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Wichgers Schreur
authors.affiliation: Department of Pediatric Immunology and Laboratory of Translational Immunology, University Medical Centre Utrecht/Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: Lotte
authors.initials: L
authors.lastname: Spel
authors.affiliation: Department of Virology, Central Veterinary Institute, part of Wageningen University and Research Centre, Lelystad, The Netherlands.
authors.forename: Rianka P M
authors.initials: RP
authors.lastname: Vloet
authors.affiliation: Department of Virology, Central Veterinary Institute, part of Wageningen University and Research Centre, Lelystad, The Netherlands.|Department of Infectious Diseases and Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Rob J M
authors.initials: RJ
authors.lastname: Moormann
authors.affiliation: Department of Pediatric Immunology and Laboratory of Translational Immunology, University Medical Centre Utrecht/Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: Marianne
authors.initials: M
authors.lastname: Boes
authors.affiliation: Department of Virology, Central Veterinary Institute, part of Wageningen University and Research Centre, Lelystad, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Kortekaas
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D015536:Down-Regulation; D015870:Gene Expression; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D012295:Rift Valley Fever / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D012296:Rift Valley fever virus / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology; D014779:Virus Replication; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D016207:Cytokines; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D007136:Immunoglobulins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D046988:Proteasome Endopeptidase Complex; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D000097802:CD83 Antigen