Molecular and reverse genetics studies of orbivirus transmission host responses epidemiology and diagnostic systems

Lead Research Organisation: University of Glasgow
Department Name: College of Medical, Veterinary &Life Sci

Abstract

Since 1998, there have been multiple incursions of bluetongue into Southern, Central and Northern Europe. These outbreaks have involved at least 12 distinct bluetongue virus (BTV) strains, belonging to 9 different serotypes and have lead to the death of more than two million animals. In addition, significant economic losses have been incurred due to loss in productivity, restrictions in animal movements and trade as part of control programmes. These events demonstrate that the entire European Union is now at risk from further introductions of BTV, and potentially of other BTV-related related Orbiviruses, particularly those also transmitted by Culicoides vectors (including African horse sickness virus [AHSV], epizootic haemorrhagic disease virus [EHDV] and equine encephalosis virus [EEV]). Worryingly, AHSV, EHDV and EEV have been detected just outside the EU in Israel, Turkey, as well as North and West Africa and now pose a further significant threat to livestock in Europe. This proposal will establish 'OrbiNet', a network of 9 laboratories focussing on research on BTV and related orbiviruses in 8 European countries and Israel. The 'OrbiNet' Partners include university departments, government laboratories and reference centres that already work on orbiviruses and associated diseases. The goals of OrbiNet are to provide training, share reagents and expertise, and conduct targeted research programmes with the overall aim to better understand orbivirus transmission, epidemiology, pathogenesis and develop better diagnostic techniques. These activities will enhance research capacity and capability and increase the knowledge base and expertise within partner laboratories, thus underpinning the development of improved tools / strategies to prevent and control these economically important animal pathogens. OrbiNet will closely liaise with the scientific community, government agencies, the EU and industry in order to exploit the knowledge generated and help to inform animal health research policies and activities at the EU level.

Technical Summary

'OrbiNet' will build a network of research laboratories across 8 European countries and Israel, focussing on bluetongue and other important diseases (including epizootic haemorhagic disease and African horse sickness) that are caused by closely related orbiviruses. The Partners include university departments, government laboratories and reference laboratories that are already established as research centres for these important and emerging pathogens. The OrbiNet coordinator, Prof. Peter Mertens, (IAH Pirbright) has 29 years BTV research experience, and is well suited to steer the network. The Principal Investigators have established and complementary expertise in molecular virology, pathogenesis, epidemiology, viral diagnostics, virus structure, vaccinology and immunology, with access to appropriate resources, facilities and reagents to meet project goals. WP leaders will meet every 6 months to monitor progress and help co-ordinate specific aspects of the programme. Exchange visits between participating laboratories, training modules, and joint meetings / publications will help disseminate results of the work carried out and cement long term relationships.

Planned Impact

The spread of BTV has had a major impact on sustainability and productivity of livestock industries across Europe. It has restricted and damaged trade between European Member states, caused major animal health losses associated with fatalities, reduced productivity and associated surveillance control programmes. BTV has been introduced on many occassions to both Southern and Northern Europe, resulting in major disease outbreaks, demonstrating that the disease poses a continuing risk to the region and indicating an increased risk posed by related orbiviral diseases transmitted by the same insect vectors. The importance of research in these areas is highlighted by the success of molecular epidemiology studies, novel assays and vaccination programmes particularly against BTV-1 and 8. However, it is clear that there is still room for further improvement in diagnostic systems, as well as a better understanding of the molecular mechanisms and genetic determinants of the host's immune response to the virus, determinants of virus transmission by the insect vector, overwintering, transplacental transmission, pathogenesis and virulence. Further detailed information in these areas will help us assess risks and develop better control strategies for bluetongue and related diseases.
 
Description Segmented viruses have genomes that are separated into multiple segments, comparable to chromosomes in higher organisms. When two segmented viruses of the same species infect the same cell, their progeny may incorporate segments picked up from the "parental" viruses. This process is called "reassortment" and represents an important way for segmented viruses to evolve. Whereas reassortment has received a lot of attention in certain segmented viruses, especially influenza A, its frequency and biological consequences remain poorly understood for most of the others. Here, we present a comprehensive analysis of the reassortment patterns in bluetongue virus, an important pathogen of livestock, during its repeated emergence in Europe in recent decades. We confirm earlier reports that reassortment is common and can involve segments derived from live vaccines used to control outbreaks. However, the mixing of viral genomes is not strictly random and reassortment is commonly followed by novel adaptive changes in the progeny virus. This points to important functional links (paired associations) between certain segments. Our findings have important implications for the classification and control of segmented viruses and generate new insights and hypotheses about the biological interactions among different parts of the bluetongue virus genome.
Exploitation Route Our findings have important implications for the classification and control of segmented viruses and generate new insights and hypotheses about the biological interactions among different parts of the bluetongue virus genome.
Sectors Agriculture, Food and Drink

 
Description BBSRC Animal Health Working Group
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description REF 2014: UoA6 Sub-panel member
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description The Pirbright Institute 
Organisation The Pirbright Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Collaborative research on the transmission and pathogenesis of bluetongue virus
Collaborator Contribution Collaborative research on the transmission and pathogenesis of bluetongue virus
Impact M. Caporale, R. Wash, A. Pini, G. Savini, P. Franchi, M. Golder, J. Patterson-Kane, P. Mertens, L. Di Gialleonardo, G. Armillotta, R. Lelli, P. Kellam and M. Palmarini (2011) "Determinants of bluetongue virus virulence in murine models of disease", Journal of Virology, 85: 11479-11489 A.E. Shaw , E. Veronesi, G. Maurin, F. Guiguen, P. Mertens, F. Rixon, S. Carpenter, M. Palmarini, C. Terzian and F. Arnaud (2012) "Drosophila melanogaster as an insect model for bluetongue virus replication and tropism", Journal of Virology, 86: 9015-9024. Caporale M, Di Gialleonorado L, Janowicz A, Wilkie G, Shaw A, Savini G, Van Rijn PA, Mertens P, Di Ventura M, Palmarini M. Virus and host factors affecting the clinical outcome of bluetongue virus infection. J Virol. 2014 Sep;88(18):10399-411. Herder V, Hansmann F, Wohlsein P, Peters M, Varela M, Palmarini M, BaumgärtnerW. Immunophenotyping of inflammatory cells associated with Schmallenberg virus infection of the central nervous system of ruminants. PLoS One. 2013 May 7;8(5):e62939.
Start Year 2010
 
Description CVR Website Updated April 2015 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact In March 2015, we embarked on a project to update our website to include up to date information about our staff, research groups and current projects. During the later half of 2014, we filmed 'talking head' interviews of our Principal Investigators to be included on their research group pages, proving interactive and engaging content for our web pages and a valuable source of information for other researchers, stakeholders, target audiences and prospective employees.



We have received very positive feedback about the developments including both internally from CVR staff but also from other research centres within the University of Glasgow who have subsequently requested advice on how we have delivered the project.

We this is a positive step, which demonstrates that we are taking the lead in promoting the CVR as a World-class centre of science research.

New interactive and up to date content, also means that visitors to our pages, spend longer looking at content and therefore, this provides a better opportunity to share information.
Year(s) Of Engagement Activity 2015
URL http://www.cvr.ac.uk
 
Description Massimo Palmarini - BBC World Service Oct 2014 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Director of the CVR, Professor Massimo Palmarini was interviewed by the BBC about his team's research on Bluetongue virus and the development of a new vaccine platform. The interview was aired on the BBC Science in Action Programme.

This interview helped to raise the profile of the publication of a CVR research paper about a new, fast track vaccine platform for Bluetongue Virus in the Journal of Virology in October 2014. We were also subsequently contacted by the BBC and asked to contribute to further interviews for a BBC Radio Scotland programme about the history of plague where our researchers were asked to explain how the study of virology has changed and developed over time.
Year(s) Of Engagement Activity 2014
URL https://www.facebook.com/centreforvirusresearch
 
Description TWIV 188 - Podcast June 2012 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Vincent Racaniello visited the CVR in 2012 to interview some of our researchers about their work in Hepatitis C virusand jaagsiekte sheep retrovirus.

The TWIV podcast is incredibly popular with followers throughout the World. This allowed us to share information about the CVR and our research to a large, digital audience.

Vincent Racaniello has since returned to work with the CVR on further podcasts. The podcast also sparked online comments and questions.
Year(s) Of Engagement Activity 2012
URL https://www.facebook.com/centreforvirusresearch