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Cytokines and their inhibitors in orf virus infection
Abstract:
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.
Insights
Orf virus causes recurrent sheep skin infections, with immunity improving over time. However, the virus employs virulence factors to evade the host immune and inflammatory responses, temporarily inhibiting protective proteins.
Area of Science:
- Veterinary Virology
- Immunology
Background:
- Orf virus (parapoxvirus) causes recurrent sheep skin infections.
- Immunity develops with reinfections, leading to smaller, faster-resolving lesions.
- Cyclosporin-A treatment negates this acquired partial immunity.
Purpose of the Study:
- To investigate the immune response to orf virus in sheep.
- To identify viral mechanisms for evading host immunity.
Main Methods:
- Analysis of cytokine mRNA in lesion biopsies (IL-1 beta, IL-3, GM-CSF, TNF-alpha, IFN-gamma).
- Characterization of immune cells (CD4+ T-cells) in draining lymph.
- Genomic analysis of orf virus for virulence factors.
Main Results:
- CD4+ T-cells in lymph are key producers of GM-CSF and IFN-gamma.
- Orf virus genome contains a VEGF homologue and an E3L-like gene, potentially enhancing virulence and inhibiting interferons.
- A GM-CSF inhibitory activity was localized to a 10 kb DNA segment of the orf virus genome.
Conclusions:
- Orf virus temporarily evades host immunity through rapid epidermal replication.
- Virulence factors produced by orf virus inhibit host immune and inflammatory responses.