Virology
Mechanisms of Immune evasion by Orf Virus and the Identification of Virulence Genes
Colin McInnes
Figure 1: The appearance of orf virus particles visualised by electron microscopy
Orf virus is a poxvirus which causes painful lesions on the skin of sheep, goats and humans. It poses a major health and welfare problem in sheep, particularly in neonatal lambs and nursing ewes, and leads to significant economic losses for the farmer. Over the past few years the incidence of orf appears to have increased, possibly as a result of the prolongation of lambing periods, the intensification of production, the increased movements of sheep, and changes in pasture management. Unfortunately, there is no specific treatment for orf once it becomes established in the animal. Recently, however we have completed an in vitro evaluation of the anti-viral drug "Cidofovir". Our findings demonstrate that this drug inhibits the growth and reproduction of Orf Virus in infected cells. Future work is planned to evaluate whether or not it can be used as an effective treatment for orf virus lesions in vivo.
With over two and a half million doses of orf-virus vaccine sold in the UK each year, vaccination remains one of the safest ways to control orf. However, current vaccines are based on fully virulent viruses which may increase the environmental pool of the virus. Work at the Moredun Research Institute is aimed at developing improved vaccines and vaccination strategies with the ultimate aim of reducing the incidence of the disease. To help us achieve this we must first understand the virus and the way in which it interacts with the animals it infects. Previously we identified a viral protein (called the GIF protein) which binds and inhibits the biological activity of granulocyte-macrophage colony-stimulating factor and interleukin-2, host proteins which are involved in the growth and maturation of cells of the immune system. Currently we are investigating the structure of the viral protein in relation to its function in an attempt to understand why it is of benefit to the virus to specifically inhibit these particular host proteins.
Figure 2: Schematic diagram showing the number of red and grey squirrels with antibodies to parapox virus according to their regional origin.
Red squirrel - No. positive/No. tested
Grey squirrel - No. positive/No. tested
In recent years it has been suggested that the decline of the red squirrel in the UK may be as a result of death caused by infection with a parapoxvirus related to orf virus. A study in red and grey squirrels of the incidence of squirrelpoxvirus infection has been completed. An assay which measures antibody to the virus revealed that 61% of apparently healthy grey squirrels have been exposed to the virus. In contrast, only 3% of red squirrels were found to have antibody to the virus, with 75% of these animals showing clinical signs of squirrelpoxvirus-associated disease. These findings are consistent with the suggestion that the virus causes little or no disease in the grey squirrels, but is highly pathogenic for the reds. In addition, we found an apparent correlation between the geographical distribution of grey squirrels with antibody to the virus and the locations where squirrelpoxvirus disease is known to, or thought to, have occurred, further supporting the hypothesis that the grey squirrel may act as a reservoir host for the virus. Future studies at the Moredun will concentrate on the characterisation of the virus itself.