Cytokines and their inhibitors in orf virus infection.

The epitheliotropic parapoxvirus, orf virus, can repeatedly infect sheep skin. A specific immune response is generated as reinfections induce smaller lesions with quicker resolution times than primary lesions. Cyclosporin-A treatment abrogates this partial immunity. Cytokine mRNAs detected in lesion biopsies include the transcripts for IL-1 beta, IL-3 GM-CSF, TNF-alpha and, less reproducibly, IFN-gamma. CD4+ T-cells predominate in afferent lymph draining the site of infection, and are the major source of GM-CSF and IFN-gamma. IL-1 beta and IL-8 are also detected. The orf virus genome contains a homologue of mammalian vascular endothelial growth factor that may enhance virulence and a vaccinia virus E3L-like gene which may inhibit the anti-viral effect of the interferons. A GM-CSF inhibitory activity has also been discovered and has been 'chased' into a 10 kb DNA segment of the orf virus genome. These studies indicate that orf virus may temporarily avoid host immunity by a combination of acute, rapid infection and replication in the epidermis and by producing virulence factors that inhibit protective proteins of the host immune and inflammatory response.