CYTOKINES AND THEIR INHIBITORS IN ORF VIRUS-INFECTION

The epitheliotropic parapoxvirus, orf virus, can repeatedly infect she ep skin. A specific immune response is generated as reinfections induc e smaller lesions with quicker resolution times than primary lesions. Cyclosporin-A treatment abrogates this partial immunity. Cytokine mRNA s detected in lesion biopsies include the transcripts for IL-1 beta, I L-3 GM-CSF, TNF-alpha and, less reproducibly, IFN-gamma. CD4(+) T-cell s predominate in afferent lymph draining the site of infection, and ar e the major source of GM-CSF and IFN-gamma. IL-1 beta and IL-8 are als o detected. The orf virus genome contains a homologue of mammalian vas cular endothelial growth factor that may enhance virulence and a vacci nia virus E3L-like gene which may inhibit the anti-viral effect of the interferons, A GM-CSF inhibitory activity has also been discovered an d has been 'chased' into a 10 kb DNA segment of the orf virus genome. These studies indicate that orf virus may temporarily avoid host immun ity by a combination of acute, rapid infection and replication in the epidermis and by producing virulence factors that inhibit protective p roteins of the host immune and inflammatory response.