Virology
Orf Infection: new developments, diagnosis and control
Dr Colin McInnes
Fig 1. Twin lambs showing characteristic orf lesions on their lips and nostrils. |
Orf has been around for centuries although the first reliable written report of it in sheep can only be traced back to 1890. It is known by a variety of names around the world, including contagious pustular dermatitis, infectious pustular dermatitis or contagious ecthyma. In Australia and New Zealand it is often referred to as “scabby mouth” however in the UK the disease is mainly known as orf.
The disease
Orf is caused by the parapoxvirus orf virus. It is related to the viruses that cause smallpox in man, myxomatosis in rabbits and swinepox in pigs, but it is a distinct virus that, under normal circumstances, is only able to infect sheep, goats or humans. The virus can only establish an infection where the skin is damaged. Most commonly, animals develop painful scabby lesions on their lips and nostrils, but in very young lambs lesions can also develop inside the mouth involving the gums, palate and tongue. Orf lesions usually resolve in four to six weeks, but within that time the lambs can transmit the virus to the ewe’s udder making her reluctant to let them suckle. As a result, mastitis and lamb starvation are a common consequence of infection. In man, infection is normally only found in those handling sheep and the most common area infected is the hands. As in sheep, the lesions will spontaneously resolve after a few weeks, but care has to be taken not to transfer the infection elsewhere or to others during this time.
Fig 2. EM of parapoxvirus orf viruses. |
Orf scabs contain millions of virus particles which, when they dry up and drop off the animal, will contaminate the environment. Lambs born into an environment contaminated with a lot of virus are more likely to develop severe oral orf, but older lambs that have been grazing in a field with a lot of thistles or stubble may also develop orf. As a consequence of the virus being shed into the environment it is important that if a farm has suffered an orf outbreak lambing sheds, troughs and feeders should be thoroughly cleaned and disinfected before they are re-used.
There is a vaccine available for helping to control orf on farms that have had a history of infection. The live vaccine is administered as a ‘scratch’ between the foreleg and the chest wall and produces a lesion and the resulting scabs contain live virus. For that reason, pregnant ewes must not be vaccinated less than seven weeks before lambing and kept away from the lambing area while the scabs are being shed.
Research progress
Fig 3. Effects of applying Cidofovir to an orf virus lesion: Cidofovir slows the development of the lesion for the first week, but eventually the lesion develops fully and is indistinguishable from the untreated lesion. |
Research at Moredun has predominantly concentrated on understanding the orf virus and how it interacts with the sheep it infects, but has also looked at ways of improving diagnosis and treatment of disease. A diagnostic test, based on the polymerase chain reaction, has been developed which should make it easier to detect an orf infection. This test will also help to distinguish field isolates of orf virus from each other and from the vaccine strain. This should improve the understanding of the epidemiology of the disease.
Cidofovir, an antiviral drug, has been used successfully to treat a case of human orf. Studies at Moredun demonstrated that although the drug is very effective at preventing growth of orf virus in the laboratory, the invivo results were not so encouraging (Figure 3). However, it is possible that it was the route of administration which was problematical rather than the drug itself not being effective. Further work will have to be done to see if this drug, or indeed other similar anti-viral drugs, offer a realistic way of helping to control orf.
Orf virus has a variety of genes which it uses to evade the sheep’s immune response to infection. By studying these processes scientists hope to learn how to combat this viral skin disease. By targeting control measures at some of these virally encoded genes it may also be possible to improve the current orf control strategies. It is known that there is a viral protein able to inhibit interferon, a key natural mediator of the sheep anti-viral immune response. Another viral protein is able to inhibit two cytokines, granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-2 (IL-2) by preventing them from binding to their native receptors on ovine cells (Figure 4). Moredun scientists are currently studying the viral proteins that are thought to interfere with the production of cytokines by infected sheep. It is hoped that by selectively removing some of the genes, encoding these proteins from the virus, or at least neutralising the proteins in some way, currently vaccines could be improved.
Fig 4. Binding analysis with a mutated form of the orf virus GM-CS/IL-2 binding protein (GIF) demonstrated that amino-acid 100 (Tryptophan) was absolutely crucial to the biological activity of the protein whereas amino acid 97 (also Tryptophan) was not crucial to the biological activity. |
This research is funded by SEERAD.