Characterization of immunostimulatory components of XXXX (parapoxvirus ovis).

@entity1 @entity5750 @entity13581 @entity41825 @entity1358 @entity379 @entity6621
Inactivated @entity13581 (ORFV, parapoxvirus ovis) induces antiviral activity in animal models of @entity41825 and exerts strong effects on @entity1 immune cells. ORFV activates @entity1358 ( @entity1358 ) via @entity5750 and, probably, Toll-like receptor signalling, and triggers the release of @entity379 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 @entity6621 /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 @entity1358 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.
