RT Journal Article SR Electronic(1) A1 Friebe, Astrid A1 Friederichs, Sonja A1 Scholz, Kai A1 Janssen, Uwe A1 Scholz, Corinna A1 Schlapp, Tobias A1 Mercer, Andrew A1 Siegling, Angela A1 Volk, Hans-Dieter A1 Weber, OlafYR 2011 T1 Characterization of immunostimulatory components of orf virus (parapoxvirus ovis) JF Journal of General Virology, VO 92 IS 7 SP 1571 OP 1584 DO https://doi.org/10.1099/vir.0.028894-0 PB Microbiology Society, SN 1465-2099, AB 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., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.028894-0