Ovine pulmonary adenocarcinoma (OPA; Jaagsiekte)

• OPA is an infectious lung cancer specific to sheep and is caused by a virus known as jaagsiekte sheep retrovirus (JSRV).
• JSRV is spread through the air by inhalation of infectious virus or direct contact with infected respiratory secretions.
• The typical symptoms 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.
• Clinical signs of OPA can take several years to develop in virus-infected sheep and there is no treatment at the present time. Due to the long incubation period between infection and disease, the number of animals in a flock that are infected with the virus may be much greater than the number that develop clinical signs of disease.
• 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.
• 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.
• Transthoracic ultrasound scanning can be used to detect sheep with small tumours before they show symptoms of clinical OPA, but reliable tests to enable detection of JSRV infection in sheep before they develop tumours are not currently available and are a focus of ongoing research.
• Protection by vaccination is a long-term goal but currently flock management methods, including test-and-cull based on the use of ultrasound scanning to identify sheep with pre-clinical OPA, offer the best approach for control.

A new project funded by the Scottish Government aims to train and develop a task force of elite vets to recognise ovine pulmonary adenocarcinoma (OPA) in sheep through ultrasound scanning (Jan 2024).

A Scottish Government OPA working group, consisting of vets, scientists, policymakers, and farmers, have developed a draft strategy for control of OPA. Moredun have secured funding from the Scottish Government to lead a pilot project to address issues raised by the industry.

OPA is an infectious lung tumour of sheep caused by Jaagsiekte Sheep Retrovirus (JSRV) causing weight loss and increasing severity of respiratory signs over several months. The disease is invariably fatal and has serious welfare implications during the latter stages. Sudden death caused by secondary bacterial infection is not uncommon. The disease is clearly of concern to flock owners and the number of cases appears to be increasing. However, there is still no robust estimate of the prevalence of OPA in Scotland.

Ultrasound scanning has been shown to be a useful tool in the control of OPA, but currently, there is a shortage of vets competent and confident in this procedure. The project aims to develop a team of vets from across Scotland with validated expertise in the control of OPA. To this end, thirteen veterinary practitioners from across Scotland have signed up for a training and research programme run by Chris Cousens (Moredun) and Phil Scott FRCVS (Capital Veterinary Services). Some of these vets already have considerable expertise in ultrasound screening for OPA, whilst some are relatively new to using this technique. All aim to become part of an elite OPA task force.

So far, the vets have completed the first training and assessment event at Moredun and a nearby farm. The vets will then work with their clients who are employing them for whole flock screening for OPA. In addition to further training opportunities, the vets will benefit from access to expert second opinions for the interpretation of ultrasound recordings. They will also submit lung samples from some of the scanned sheep for diagnostic confirmation which will provide independent validation of the vet’s scanning results.

OPA-affected flocks participating in this study are expected to see a marked reduction in annual OPA incidence over the two years study and beyond, whilst those not affected by OPA should benefit from two years of evidence supporting a low-risk OPA status.

To maximise the outputs of the funding, Moredun are collecting additional information about OPA and the performance of flocks before, during and after the implementation of OPA control measures to assess how this could increase farm efficiency and reduce greenhouse gas emissions. A further part of the study will assess whether a simple blood test would be a useful adjunct to increase the specificity of ultrasound scanning for OPA.

This new pilot study complements other research at Moredun aimed at gaining a better understanding of the transmission of JSRV and the development of OPA. This knowledge will also help to deliver practical solutions applicable to real life sheep farming.

For more information, contact Chris Cousens: Chris.Cousens@moredun.ac.uk

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.

Scottish Government

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.

Moredun Scientific

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.