Scientists at The Pirbright Institute have collaborated with the MRC Laboratory of Molecular Biology and other research institutes* to uncover a new system used by the foot-and-mouth disease virus (FMDV) to prevent antiviral signalling of infected cells. The discovery could allow scientists to detect animals that have been infected with FMDV and distinguish them from those that have been vaccinated.
It is essential that countries vaccinating against FMD are able to discriminate between vaccinated and infected animals in order to maintain their ability to trade. The new research published in Proceedings of the National Academy of Sciences describes a novel biomarker that could be valuable for use in such detection methods.
Virus infected cells deploy an antiviral protein called ISG15, which is able to attach to FMDV proteins and prevent replication. FMDV encodes a protein called Lbpro, which was found to cut ISG15 to stop its action, therefore allowing the virus to continue replicating unhindered. Importantly, the cutting of ISG15 leaves small parts of protein behind (a GlyGly motif) that can be detected by scientists, and could potentially allow them to show that an animal is infected.
Dr Toby Tuthill, head of the Picornavirus Molecular Biology group, said: “Discovering the unique interaction between Lbpro and ISG15 has given us new insights into the arms race between the host and FMDV. One of the more exciting opportunities it presents us with is the possibility of using GlyGly for the purpose of detection, the key advantage being that GlyGly is only made when an animal is infected by FMDV. An animal that has been vaccinated will not create GlyGly and therefore could allow the two to be distinguished.”
Dr David Komander from MRC Laboratory of Molecular Biology said: “Our discovery of this new mechanism immediately led to a testable biological hypothesis that could be confirmed by researchers at Pirbright and Kuppefeld lab in Utrecht. We are very excited to take this forward, and potentially develop new FMDV diagnostics based on our work.”
Providing another method that can accurately determine if herds are infected could improve the ability of vaccinating countries to trade, thereby helping to ease the economic burden imposed by FMD.
*This research was carried out in collaboration with the MRC Laboratory of Molecular Biology, Cambridge; Max F. Perutz Laboratories, University of Vienna; Faculty of Veterinary Medicine, Utrecht University and Leiden University Medical Center.
ENDS
Notes to editors:
FMD is a highly infectious disease that infects cloven hooved (two-toed) animals such as cattle, sheep and pigs. The virus causes fever, lesions in the mouth and hooves and a loss in growth and milk production. The global annual economic loss is estimated to be between $6.5-$21 billion USD.
Please visit Pirbright’s FMD virus page and watch the Institute’s animation video to learn more about the disease.
For more information please contact communications@pirbright.ac.uk Tel: +44 (0) 1483 231120.
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About The Pirbright Institute
The Pirbright Institute is a world leading centre of excellence in research and surveillance of virus diseases of farm animals and viruses that spread from animals to humans. Based in the UK and receiving strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC), the Institute works to enhance capability to contain, control and eliminate these economically and medically important diseases through highly innovative fundamental and applied bioscience.
With an annual income of nearly £26.1 million from grants and commercial activity, and a total of £5 million strategic investment from BBSRC during 2016-2017, the Institute contributes to global food security and health, improving quality of life for animals and people.
For more information about The Pirbright Institute see: www.pirbright.ac.uk
About MRC Laboratory of Molecular Biology
The Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) is one of the world's leading research institutes. Discoveries and inventions developed at the LMB, for example DNA sequencing and methods to determine the structure of proteins, have revolutionised all areas of biology. Its scientists work to advance understanding of biological processes at the molecular level. This information will help us to understand the workings of complex systems, such as the immune system and the brain, and solve key problems in human health. http://www2.mrc-lmb.cam.ac.uk/
About BBSRC
BBSRC invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond.
Funded by government, BBSRC invested £469 million in world-class bioscience in 2016-17. We support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.
More information about BBSRC, our science and our impact: https://bbsrc.ukri.org
More information about BBSRC strategically funded institutes: https://bbsrc.ukri.org/research/institutes/strategically-funded-institutes/