About Ovine pulmonary adenocarcinoma (OPA; Jaagsiekte)
Ovine pulmonary adenocarcinoma (OPA, also known as jaagsiekte) is an infectious and fatal lung disease of sheep. It is caused by a virus, known as jaagsiekte sheep retrovirus (JSRV), which infects cells in the lung making them form tumours. The tumour cells then produce more of the virus which can infect new areas of the lung or other sheep.
The disease signs associated with OPA are loss of condition, difficulty breathing and, in around half of cases, production of clear or frothy fluid from the affected lungs appearing as discharge dripping or pouring from the nose. The sheep may survive for many weeks after the signs of disease appear or may die suddenly. In affected flocks OPA may be the cause of death of 1% to 20% of the flock in one year. Additional productivity losses such as reduced fertility have yet to be investigated. It is important to note that the early stages of OPA are not apparent as the tumours are too small to cause any breathing problems even though they are able to produce virus which can infect other sheep.
Although OPA was first described almost 200 years ago, methods for controlling the disease are limited. However, in recent years, great progress has been made in understanding how the virus triggers the growth of the cancer in the lung and research is advancing in the area of early diagnostics.
- OPA (jaagsiekte) is an infectious lung cancer specific to sheep and is caused by a virus (jaagsiekte sheep retrovirus).
- OPA is a common disease in many sheep-rearing countries including the UK.
- The jaagsiekte retrovirus is spread through the air by inhalation of infectious virus or direct contact with infected respiratory secretions. The virus may also be spread from ewe to lamb through milk or colostrum.
- The typical signs of OPA are difficulty in breathing, often with marked weight loss. A feature unique to OPA is the over-production of fluid in the lungs, which in some animals is apparent as a watery discharge from the nose. The disease is invariably fatal and there is no treatment at the present time.
- There is a very long incubation period between infection and the development of disease. The number of animals in a flock that are infected with the virus may therefore be much greater than the number that develop clinical signs of disease during their commercial lifespan.
- Animals suspected to be affected should be isolated from the flock and a vet contacted. Post mortem examination of the lungs is advised in order to confirm the diagnosis.
- Currently there is no strong evidence for breed differences in susceptibility to OPA.
- OPA is commonly introduced into new flocks through the purchase of apparently healthy animals that are carrying the virus.
- Tests to enable detection of infection in sheep before they develop clinical signs of OPA are a focus of ongoing research. Ultrasound scanning can identify early OPA in sheep before any signs of disease begin to show and whilst the animal is still of some cull value. Unfortunately ultrasound cannot give a definitive negative result for individual animals.
- Protection by vaccination is a long-term goal but currently flock management methods offer the best approach for control.
Current interests and future aims
- Development of improved methods for early diagnosis of OPA. This includes the identification of diagnostic biomarkers in blood and nasal swabs of sheep and the detection of early OPA tumours using ultrasound. We are now determining the sensitivity and specificity of the ultrasound screen and testing whether using ultrasound as the basis of a screen-and-cull programme in OPA-affected flocks will be an effective way to reduce the disease incidence in future years.
- Understanding the pathogenesis of OPA through profiling of gene expression in OPA and identification of cellular pathways that contribute to disease.
- Determining the role of the local inflammatory response to tumour growth and disease progression in OPA.
- Development of in vitro methods for modelling early events in JSRV transformation. This includes the development of cell lines that support JSRV replication and the generation of an ovine lung slice culture model for analysis of JSRV Env-mediated transformation.
Moredun is conducting research on ovine pulmonary adenocarcinoma within the Scottish Government Strategic Research Programme (2016-2021) to develop new diagnostic tests and to examine JSRV replication in cell culture based systems and in infected sheep.
Agriculture and Horticulture Development Board and Hybu Cig Cymru – Meat Promotion Wales
Detecting JRSV in a Thin Ewe Diagnostic Package (2015-Oct 2016)
This pilot project showed that the RT-qPCR test on nasal swabs collected from 20 thin ewes may have a useful application as a screening test to determine flock status for OPA. Further work will be required to bring the test to market including scale-up of validation and further streamlining of processes to make the test commercially viable.
Clyde Wind Farm Community and Development Fund, Upper Clyde Farmers Club and Scottish Government
Supporting the sustainability of farming in the CWF area by reducing the impact of a major disease problem of sheep (Feb 2017-Jan 2020).
This programme aims to reduce the commercial impact of OPA on sheep farms by the use of ultrasound scanning to detect pre-clinical OPA and allowing culling whilst the animals are still of some commercial value. It will determine whether the screen-and-cull method is effective at reducing the incidence of OPA year on year and whether it is economically advantageous to the flocks involved.
Biotechnology and Biological Sciences Research Council
Dissecting the pathogenesis of ovine pulmonary adenocarcinoma with RNA-Seq. (2014-2017).
Together with colleagues at the Roslin Institute, we are performing comprehensive analysis of gene expression in OPA. The cellular pathways altered by virus infection and subsequent tumour growth are being characterised further using in vitro cell culture and lung tissue culture systems. Our goal is to identify new avenues for research into OPA that will lead to new strategies for controlling the disease.
The role of microRNAs in the host response to infection in ruminants (2016-2019).
A PhD Student sponsored by Moredun Scientific is analysing the role of microRNAs in OPA pathogenesis and evaluating their potential as diagnostic markers for this disease. This work will encompass other ruminant diseases including Johne’s disease.