title: Characterization of immunostimulatory components of orf virus (parapoxvirus ovis).
abstract: Inactivated orf virus (ORFV, parapoxvirus ovis) induces antiviral activity in animal models of acute and chronic viral infections and exerts strong effects on human immune cells. ORFV activates antigen presenting cells (APC) via CD14 and, probably, Toll-like receptor signalling, and triggers the release of IFN-γ that has been identified as the key mediator of the antiviral activity. After delineating virus proteins as being the most likely active constituent, we aimed to characterize the ORFV proteins responsible for the therapeutic effect. By using a vaccinia virus/ORFV expression library we identified several multi-gene DNA fragments with strong immunomodulatory activity. Together these fragments contain 27 ORFs. The encoded proteins are related to virion structure and transcription but are otherwise unrelated. Two proteins were separately expressed and purified, and demonstrated immunostimulatory activity. Gene expression profiles induced by ORFV and the identified fragments were investigated by microarray analysis. Interestingly, all active fragments induced a similar gene-expression pattern, differing only in quantitative aspects. Obviously, several proteins of ORFV activate similar cellular pathways, modulating APC to generate a strong T-helper 1-dominated immune response. This was balanced by additional induction of immune dampening mechanisms, suggesting regulatory differences compared to single cytokine therapies. We conclude that ORFV may have the potential to enrich the armamentarium of antiviral therapies.
authors.affiliation: Institute of Medical Immunology and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Friebe
authors.affiliation: Bayer HealthCare AG, Leverkusen, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Friederichs
authors.affiliation: Bayer HealthCare AG, Leverkusen, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Scholz
authors.affiliation: Miltenyi Biotec GmbH, Cologne, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Janssen
authors.affiliation: Miltenyi Biotec GmbH, Cologne, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Scholz
authors.affiliation: Bayer HealthCare AG, Leverkusen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Schlapp
authors.affiliation: University of Otago, Dunedin, New Zealand.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mercer
authors.affiliation: Bayer HealthCare AG, Leverkusen, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Siegling
authors.affiliation: Institute of Medical Immunology and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.affiliation: Bayer HealthCare AG, Leverkusen, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Weber
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002417:Cattle; D002460:Cell Line; D004474:Ecthyma, Contagious / Q000276:immunology* / Q000821:virology; D005260:Female; D006801:Humans; D051379:Mice; D009923:Orf virus / Q000235:genetics / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D014764:Viral Proteins