Expression and formulation of Bluetongue virus genes and proteins for development of effective vaccination strategies

Lead Research Organisation: The Pirbright Institute
Department Name: UNLISTED

Abstract

Bluetongue virus (BTV) can infect all ruminants, including cows, sheep and goats, in most cases without causing disease. However, when the virus infects sheep, particularly the European breeds, it can cause severe disease, killing up to 70% of the infected animals. The virus is transmitted by biting midges (Culicoides species), particularly those species which prefer warmer climates. As a result of recent changes in the European climate that are thought to have been caused by global warming, midges that can transmit BTV are moving northwards. This places Europe at much greater risk from the disease than before. Indeed, since 1998, six different strains of BTV have invaded the Mediterranean region, on a total of seven different occassions, affecting all of the countries of Southern Europe and collectively causing the largest outbreak of the disease ever recorded (with over 1.5 million dead animals). The vaccines that are currently available to fight bluetongue are live strains of the bluetongue virus that have been weakened (attenuated) by growth for many generations in cell cultures. These are supposed to produce only mild symptoms but protect the animal from more dangerous virus strains. However, there is evidence that these vaccine strains are also dangerous, causing disease and being transmitted by the same biting midges as the wild type viruses. Alternative inactivated vaccines have recently become available, based on partially purified and chemically treated virus, although the nature of the response to these vaccines (protective or not) still has to be tested in the field. The bluetongue virus particle has an outer protein layer composed of two proteins, VP2 and VP5, and a core, with a surface composed of VP7, proteins which are recognised by the immune system of infected animals, generating a reponse that can protect against the disease. The project will make DNA copies of viral genes and use them to synthesise viral proteins in bacteria, or in insect cells. The proteins will then be purified and used to study their interactions with the animal's immune system, particularly the production of a protective response e.g. antibodies that can neutralise the virus. The project will also examine the structure of the outer surface proteins of BTV particles, to see which aminoacid sequences react with the immune system and lead to a neutralising response. The project will use DNA copies of the viral genes directly, or copied into another virus (vaccinia virus - MVA), to synthesise the BTV proteins in vaccinated animals and thus ativating their immune system. By incorporating the synthesised and purified viral proteins, DNAs or MVA into microscopic synthetic beads that breakdown over time in a controlled way. This should prolong the exposure of the animals to the vaccine, allowing more time to generate a higher level of protection against the virus, and therefore better protection against the disease. These new vaccination strategies are considered to be entirely safe, since they do not use live BTV to induce immunity/protection. They will therefore be used in different combinations to see which is most effective, and to design a better (and safer) vaccine. Because of the promise shown by these new types of vaccines, we will use this opportunity to study in more detail how they work. We want to find out if the position of the proteins on or in the beads affects the way the immune system responds to them. At the same time, we want to study which gives the best response : the use of each component on a single bead system, or beads containg different proteins and/or DNAs. Our ultimate goal being a vaccine that is 100% efficient after a single dose.

Technical Summary

Since 1998, five serotypes of bluetongue virus (BTV) have invaded southern and central Europe, killing over 1.5 million sheep. The virus is transmitted by biting midges (Culicoides spp.) which are most active and abundant in warm climates. As a result of climate change, both vectors and virus have expanded progressively northwards and westwards within Europe. The live attenuated vaccines currently available (developed in South Africa) are not suitable for European breeds of sheep (causing disease, abortion, foetal malformation) and are not recommended for cattle or goats (alternative host species). The other potential vaccine candidates already available, include baculovirus-expressed virus like particles (VLP) and inactivated virus preparations, although questions remain concerning their relative cost, efficacy in the field or safety of inactivation processes. We will use established technologies to express BTV capsid proteins (VP2, VP5 and VP7) in bacteria and insect cells (recombinant baculovirus). The open reading frames of relevant genome segments (Seg-2, -6 and -7) of representative European BTV strains will be converted to full length cDNA using terminal primers. These will be cloned into IPTG-inducible T7 promoter plasmids and expressed as hexa-His-tagged fusion proteins, initially in the Origami E.coli strain (for optimal disulphide bond formation believed important for VP2). The His-tagged recombinant proteins will be purified using affinity chromatography on 'nickel' columns (AKTA purification system). The BTV cDNAs will also be inserted into i) the pFastBac vector (Invitrogen) to facilitate the generation of recombinant baculoviruses, ii) a recombinant vaccinia virus (Ankara strain - MVA), considered safe in humans and other animals (viral DNA vaccine) and iii) the high-yield transgene-producing plasmid gWIZ (Gene Therapy Systems) harbouring an optimised human cytomegalovirus (CMV) expression cassette and intopCI-neo ( Promega), (for non-viral DNA vaccine). The expressed fusion proteins will be purified using affinity chromatography on 'nickel' columns (AKTA purification system). The pCI-neo Vector contains the neomycin phosphotransferase gene, a selectable marker for mammalian cells and can be used for transient expression or for stable expression by selecting transfected cells with the antibiotic G-418. The BTV outer capsid and cell attachment protein VP2, is also the major neutralisation antigen. It can be cleaved into a number of polypeptides by proteinases, generating infectious subviral particles (ISVP). However, ISVP retain the ability to interact with neutralising antibodies and full infectivity for mammalian cells, but also have an enhanced infectivity (x1000) for Culicoides cells. VP2 cleavage products will be characterised by mass spectroscopy, to identify cleavage sites; recombinants will also be expressed and purified as described above, and used to study their interaction with neutralising antibodies. The expressed outer capsid proteins (VP2 and VP5), and the cleavage products of VP2 and VP7, will be used to raise an immune response, initially in mice. The project will analyse the contribution of each arm of the immune system in protection. We will incorporate recombinant BTV proteins and/or DNA vaccines into polymeric carrier systems to generate non-viral particulate vaccines. Controlled release of antigen or DNA, will be used to achieve prolonged exposure of the immune system to the vaccine, stimulating a secondary immunisation and, improving immunity. During these studies we will investigate the influence of specific polymeric carrier systems, and the effect of i) protein localisation on/in the polymer matrix on immune response bias and ii) formulation of protein and/or DNA-encoded antigens or co-administration of these and/or MVA vaccines
 
Description BBSRC has indicated that they do not require a response
Exploitation Route BBSRC has indicated that they do not require a response
Sectors Agriculture, Food and Drink

 
Description BBSRC has indicated that they do not require a response
Sector Agriculture, Food and Drink
Impact Types Economic

 
Description "Understanding pathogen, livestock, environment interactions involving bluetongue virus" (PALE-Blu)
Amount € 6,300,000 (EUR)
Funding ID 727393-2 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 06/2016 
End 11/2020
 
Description PALE-Blu H20:20 grant "Understanding pathogen, livestock, environment interactions involving bluetongue virus" 
Organisation Agricultural Research for Development (CIRAD)
Country France 
Sector Public 
PI Contribution Peter Mertens is coordinator of the PALE-Blu H20:20 consortium. My group is also directly involved in most of the work packages that are included in the grant.
Collaborator Contribution Bluetongue is an economically important disease that since 1998 has invaded Europe, particularly southern and central countries. These changes are thought to be linked to climate change and appear unlikely to be reversed. The disease causes caused economic losses due to fatalities in livestock (>25% in sheep), loss of reproductive performance and milk/meat production, and restrictions in animal movements and trade. 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. 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 continuos 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.
Impact The BTV Glue database (http://btv.glue.cvr.ac.uk/#/home) Publications are in preparations from the PALE-Blu consortium Scientific meetings have been organised in Glasgow, Rabat and Brussels.
Start Year 2016
 
Description PALE-Blu H20:20 grant "Understanding pathogen, livestock, environment interactions involving bluetongue virus" 
Organisation Complutense University of Madrid
Country Spain 
Sector Academic/University 
PI Contribution Peter Mertens is coordinator of the PALE-Blu H20:20 consortium. My group is also directly involved in most of the work packages that are included in the grant.
Collaborator Contribution Bluetongue is an economically important disease that since 1998 has invaded Europe, particularly southern and central countries. These changes are thought to be linked to climate change and appear unlikely to be reversed. The disease causes caused economic losses due to fatalities in livestock (>25% in sheep), loss of reproductive performance and milk/meat production, and restrictions in animal movements and trade. 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. 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 continuos 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.
Impact The BTV Glue database (http://btv.glue.cvr.ac.uk/#/home) Publications are in preparations from the PALE-Blu consortium Scientific meetings have been organised in Glasgow, Rabat and Brussels.
Start Year 2016
 
Description PALE-Blu H20:20 grant "Understanding pathogen, livestock, environment interactions involving bluetongue virus" 
Organisation Friedrich Loeffler Institute
Country Germany 
Sector Public 
PI Contribution Peter Mertens is coordinator of the PALE-Blu H20:20 consortium. My group is also directly involved in most of the work packages that are included in the grant.
Collaborator Contribution Bluetongue is an economically important disease that since 1998 has invaded Europe, particularly southern and central countries. These changes are thought to be linked to climate change and appear unlikely to be reversed. The disease causes caused economic losses due to fatalities in livestock (>25% in sheep), loss of reproductive performance and milk/meat production, and restrictions in animal movements and trade. 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. 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 continuos 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.
Impact The BTV Glue database (http://btv.glue.cvr.ac.uk/#/home) Publications are in preparations from the PALE-Blu consortium Scientific meetings have been organised in Glasgow, Rabat and Brussels.
Start Year 2016
 
Description PALE-Blu H20:20 grant "Understanding pathogen, livestock, environment interactions involving bluetongue virus" 
Organisation International Livestock Research Institute (ILRI)
Country Kenya 
Sector Charity/Non Profit 
PI Contribution Peter Mertens is coordinator of the PALE-Blu H20:20 consortium. My group is also directly involved in most of the work packages that are included in the grant.
Collaborator Contribution Bluetongue is an economically important disease that since 1998 has invaded Europe, particularly southern and central countries. These changes are thought to be linked to climate change and appear unlikely to be reversed. The disease causes caused economic losses due to fatalities in livestock (>25% in sheep), loss of reproductive performance and milk/meat production, and restrictions in animal movements and trade. 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. 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 continuos 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.
Impact The BTV Glue database (http://btv.glue.cvr.ac.uk/#/home) Publications are in preparations from the PALE-Blu consortium Scientific meetings have been organised in Glasgow, Rabat and Brussels.
Start Year 2016
 
Description PALE-Blu H20:20 grant "Understanding pathogen, livestock, environment interactions involving bluetongue virus" 
Organisation Kafkas University
PI Contribution Peter Mertens is coordinator of the PALE-Blu H20:20 consortium. My group is also directly involved in most of the work packages that are included in the grant.
Collaborator Contribution Bluetongue is an economically important disease that since 1998 has invaded Europe, particularly southern and central countries. These changes are thought to be linked to climate change and appear unlikely to be reversed. The disease causes caused economic losses due to fatalities in livestock (>25% in sheep), loss of reproductive performance and milk/meat production, and restrictions in animal movements and trade. 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. 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 continuos 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.
Impact The BTV Glue database (http://btv.glue.cvr.ac.uk/#/home) Publications are in preparations from the PALE-Blu consortium Scientific meetings have been organised in Glasgow, Rabat and Brussels.
Start Year 2016
 
Description PALE-Blu H20:20 grant "Understanding pathogen, livestock, environment interactions involving bluetongue virus" 
Organisation Kimron Veterinary Institute
PI Contribution Peter Mertens is coordinator of the PALE-Blu H20:20 consortium. My group is also directly involved in most of the work packages that are included in the grant.
Collaborator Contribution Bluetongue is an economically important disease that since 1998 has invaded Europe, particularly southern and central countries. These changes are thought to be linked to climate change and appear unlikely to be reversed. The disease causes caused economic losses due to fatalities in livestock (>25% in sheep), loss of reproductive performance and milk/meat production, and restrictions in animal movements and trade. 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. 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 continuos 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.
Impact The BTV Glue database (http://btv.glue.cvr.ac.uk/#/home) Publications are in preparations from the PALE-Blu consortium Scientific meetings have been organised in Glasgow, Rabat and Brussels.
Start Year 2016
 
Description PALE-Blu H20:20 grant "Understanding pathogen, livestock, environment interactions involving bluetongue virus" 
Organisation National Veterinary Institute
Country Sweden 
Sector Public 
PI Contribution Peter Mertens is coordinator of the PALE-Blu H20:20 consortium. My group is also directly involved in most of the work packages that are included in the grant.
Collaborator Contribution Bluetongue is an economically important disease that since 1998 has invaded Europe, particularly southern and central countries. These changes are thought to be linked to climate change and appear unlikely to be reversed. The disease causes caused economic losses due to fatalities in livestock (>25% in sheep), loss of reproductive performance and milk/meat production, and restrictions in animal movements and trade. 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. 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 continuos 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.
Impact The BTV Glue database (http://btv.glue.cvr.ac.uk/#/home) Publications are in preparations from the PALE-Blu consortium Scientific meetings have been organised in Glasgow, Rabat and Brussels.
Start Year 2016
 
Description PALE-Blu H20:20 grant "Understanding pathogen, livestock, environment interactions involving bluetongue virus" 
Organisation The Pirbright Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Peter Mertens is coordinator of the PALE-Blu H20:20 consortium. My group is also directly involved in most of the work packages that are included in the grant.
Collaborator Contribution Bluetongue is an economically important disease that since 1998 has invaded Europe, particularly southern and central countries. These changes are thought to be linked to climate change and appear unlikely to be reversed. The disease causes caused economic losses due to fatalities in livestock (>25% in sheep), loss of reproductive performance and milk/meat production, and restrictions in animal movements and trade. 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. 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 continuos 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.
Impact The BTV Glue database (http://btv.glue.cvr.ac.uk/#/home) Publications are in preparations from the PALE-Blu consortium Scientific meetings have been organised in Glasgow, Rabat and Brussels.
Start Year 2016
 
Description PALE-Blu H20:20 grant "Understanding pathogen, livestock, environment interactions involving bluetongue virus" 
Organisation University Libre Bruxelles (Université Libre de Bruxelles ULB)
Country Belgium 
Sector Academic/University 
PI Contribution Peter Mertens is coordinator of the PALE-Blu H20:20 consortium. My group is also directly involved in most of the work packages that are included in the grant.
Collaborator Contribution Bluetongue is an economically important disease that since 1998 has invaded Europe, particularly southern and central countries. These changes are thought to be linked to climate change and appear unlikely to be reversed. The disease causes caused economic losses due to fatalities in livestock (>25% in sheep), loss of reproductive performance and milk/meat production, and restrictions in animal movements and trade. 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. 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 continuos 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.
Impact The BTV Glue database (http://btv.glue.cvr.ac.uk/#/home) Publications are in preparations from the PALE-Blu consortium Scientific meetings have been organised in Glasgow, Rabat and Brussels.
Start Year 2016
 
Description PALE-Blu H20:20 grant "Understanding pathogen, livestock, environment interactions involving bluetongue virus" 
Organisation University of Glasgow
Department MRC - University of Glasgow Centre for Virus Research
Country United Kingdom 
Sector Academic/University 
PI Contribution Peter Mertens is coordinator of the PALE-Blu H20:20 consortium. My group is also directly involved in most of the work packages that are included in the grant.
Collaborator Contribution Bluetongue is an economically important disease that since 1998 has invaded Europe, particularly southern and central countries. These changes are thought to be linked to climate change and appear unlikely to be reversed. The disease causes caused economic losses due to fatalities in livestock (>25% in sheep), loss of reproductive performance and milk/meat production, and restrictions in animal movements and trade. 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. 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 continuos 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.
Impact The BTV Glue database (http://btv.glue.cvr.ac.uk/#/home) Publications are in preparations from the PALE-Blu consortium Scientific meetings have been organised in Glasgow, Rabat and Brussels.
Start Year 2016
 
Description PALE-Blu H20:20 grant "Understanding pathogen, livestock, environment interactions involving bluetongue virus" 
Organisation University of Nottingham
Department School of Veterinary Medicine and Science Nottingham
Country United Kingdom 
Sector Academic/University 
PI Contribution Peter Mertens is coordinator of the PALE-Blu H20:20 consortium. My group is also directly involved in most of the work packages that are included in the grant.
Collaborator Contribution Bluetongue is an economically important disease that since 1998 has invaded Europe, particularly southern and central countries. These changes are thought to be linked to climate change and appear unlikely to be reversed. The disease causes caused economic losses due to fatalities in livestock (>25% in sheep), loss of reproductive performance and milk/meat production, and restrictions in animal movements and trade. 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. 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 continuos 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.
Impact The BTV Glue database (http://btv.glue.cvr.ac.uk/#/home) Publications are in preparations from the PALE-Blu consortium Scientific meetings have been organised in Glasgow, Rabat and Brussels.
Start Year 2016
 
Description PALE-Blu H20:20 grant "Understanding pathogen, livestock, environment interactions involving bluetongue virus" 
Organisation Veterinary School of Alfort
PI Contribution Peter Mertens is coordinator of the PALE-Blu H20:20 consortium. My group is also directly involved in most of the work packages that are included in the grant.
Collaborator Contribution Bluetongue is an economically important disease that since 1998 has invaded Europe, particularly southern and central countries. These changes are thought to be linked to climate change and appear unlikely to be reversed. The disease causes caused economic losses due to fatalities in livestock (>25% in sheep), loss of reproductive performance and milk/meat production, and restrictions in animal movements and trade. 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. 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 continuos 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.
Impact The BTV Glue database (http://btv.glue.cvr.ac.uk/#/home) Publications are in preparations from the PALE-Blu consortium Scientific meetings have been organised in Glasgow, Rabat and Brussels.
Start Year 2016