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.
Haig
D
D
Moredun Research Institute, Edinburgh, UK.
McInnes
C
C
Deane
D
D
Lear
A
A
Myatt
N
N
Reid
H
H
Rothel
J
J
Seow
H F
HF
Wood
P
P
Lyttle
D
D
Mercer
A
A
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000276:immunology*; D004474:Ecthyma, Contagious / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D009923:Orf virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D012756:Sheep; D012867:Skin / Q000276:immunology; D014774:Virulence / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
D016207:Cytokines; D016572:Cyclosporine