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Understanding pathogen, livestock, environment interactions involving bluetongue virus

Periodic Reporting for period 2 - PALE-Blu (Understanding pathogen, livestock, environment interactions involving bluetongue virus)

Reporting period: 2018-12-01 to 2019-11-30

Bluetongue is an economically important disease that since 1998 has invaded Europe, particularly southern and central countries. These changes linked to climate change appear unlikely to be reversed. The disease causes major economic losses due to fatalities in livestock (>25% in sheep), loss of reproductive performance and milk/meat production, restrictions in animal movements and trade and costs of control measures.
The PALE-Blu Project brings together 19 different Partner organisations in fifteen countries to generate data concerning the distribution and interaction of genetic variants of the bluetongue virus with insect vector and host populations to inform control and prevention strategies
The project will analyse interactions between different virus strains, insect vectors and vertebrate hosts at the population, individual and molecular levels., Transmission mechanisms will be analysed to inform the ways in which risks can be evaluated, modelled and mitigated.
In particular the project will identify and map different virus and vector populations and the environmental factors that determine their incidence and distribution to understand how genetic variations can determine transmission of different BTV serotype / strains in different regions. Databases will be created to help in the global identification of different BTV variants based on sequence analyses.
The project will develop diagnostic assays to maintain and improve current diagnostic and surveillance capabilities. These will specifically include the recently identified ‘novel’ serotypes (BTV-25 upwards) to ensure that they can also be rapidly and sensitively detected.
The project will seek to generate additional cell lines for European and Africa Culicoides species for further studies of transmission mechanisms and differences between different vector populations / species.
Cross reactive antigens and epitopes will be identified for different BTV serotypes to develop safe multivalent or cross-reactive vaccines against different BTV serotypes
The project will develop and maintain communication and project management through websites periodic meetings and publications / presentations to both scientific and lay audiences.
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BTV sequences have been collected, annotated and curated and introduced into the BTV-GLUE website. The beta version of the BTV-GLUE dataset is available via a public web server (http://btv.glue.cvr.ac.uk). We are currently inserting an automated genotyping tool for all segments.
A comprehensive database of Culicoides vector abundance, covering most of Europe and neighbouring countries, has been generated to define epizones with different insect vector populations. Livestock maps (cattle, sheep, and goats) updated to reflect 2010 have helped define epizones based on ecoclimatic data.
Diagnostic tools for the novel BTV serotypes, as well as multiplexed assay systems are being developed and evaluated
Primary cell lines for additional Culicoides species, have been developed and will be maintained in order to develop continuous cell lines.
Rescued mono-reassortant BTV strains have been generated to explore the molecular basis for contact transmission and insect vector transmission as well as and other viral properties, including interactions with the innate immune response and inhibition by interferon.
Antiviral activity of statin derivatives and calcium channel inhibitors, will be further explored
Project outputs and data are being and will continue to be disseminated through one or more of the four websites that have been established or associated with the project:
http://www.paleblu.eu/ : the general project website, which provides project details, presentations, publications and deliverables
This includes the kick off project meeting in Glasgow 2017: http://www.paleblu.eu/system/files/2019-01/2017-09-06-MeetingReportFor1stPALE-BluMeetingCVRGlasgow-LR%20update.pdf
and the 2nd meeting in Rabat 2018: http://www.paleblu.eu/system/files/2019-01/2018-09-19-20-2ndPALE-BluMeetingMorocco.pdf
http://btv.glue.cvr.ac.uk/#/home : the project website which hosts datacentric software package which includes sequence data, genome annotations and bioinformatic analysis tools. See WP1 above
https://www.edenextdata.com/: the project spatial data archive, see also WP3 above.
http://mapserver.izs.it/gis_oiemaps/: a site which displays global BTV distributions.

A newly developed haploid embryonic stem cell library, is being used to characterize cellular genes and pathways essential for productive BTV-8 infection.
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BTV-GLUE will help the BTV community to study BTV biology, evolution and outbreaks to distinguish the properties of BTV strains circulating worldwide.
The addition of the Culicoides distribution data to epizone maps already developed, will identify risk areas for BTV transmission. A model of wind-borne Culicoides movements will help to characterise natural barriers to vector dispersion. Collectively these models will help us understand pathways and risk factors in BTV incursions and epidemiology.
Work is ongoing to maintain a comprehensive set of diagnostic assays to detect current and known BTV serotypes that represent outbreak risks. Work is also progressing towards multiplexing assays using novel platforms like MagPlex to automate throughput. Recent developments in sequencing technologies provide opportunities to identify viral pathogens using a metagenomics approach.
Development cell lines from additional midge species will aid our understanding of the molecular characteristics that determine if a particular midge species is a competent vector for a specific BTV strain.
Investigations of viral genetic control of infection, replication and vector competence in European Culicoides species will enhance our understanding of viral, insect and host factors that enable BTV insect-transmission. This may help us to predict vector transmissibility of BTV strains directly by interrogation of the virus genome.
Identification of virus-related genetic control of horizontal transmission (HT) in the ruminant host might allow us to predict non-vector transmissibility of BTV strains by interrogation of the virus genome. The data obtained will improve control measures and provide advice to policy makers concerning the risks posed by novel BTV strains
The development of a library of BTV specific monoclonal antibodies for BTV, will support the identification of VP2 regions / epitopes involved in the protective response. They may also facilitate the development of serotype specific serological assays (e.g. ELISA). The generation and validation of novel vaccines, vaccination strategies and antivirals that are compatible with existing surveillance methods/assays and potentially ‘cross-serotype’ will enhance our ability to respond rapidly to disease incursions.
Developing effective and broad-range antiviral strategies for dsRNA viruses using the orbiviruses, could be a step towards controlling dsRNA virus replication in infected animals, including potentially humans.
The PALE-Blu websites provide project related data to project members. They have a combined hit rate in excess of 3000/month.The project will also generate fact-sheets, regular e-newsletters and a short series of videos describing project outputs and impact. Like the websites, these will be aimed at a wide audience, not just professionals and planners.
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