Elucidating local and systemic immune responses of livestock to arbovirus infections and arthropod saliva.
Lead Research Organisation:
The Pirbright Institute
Department Name: UNLISTED
Abstract
This interdisciplinary research project will study the immune response and pathogenesis of arboviral infections in their mammalian hosts while additionally addressing the effect of vector arthropod saliva. The majority of studies investigating the immune response towards arboviruses and vector arthropod saliva will be carried out using their natural mammalian host, either in vivo or by establishing primary and/or ex vivo cell and organ culture systems. A major aspect of the in-vivo studies will be the cannulation of superficial lymphatic vessels in cattle and sheep to compare the inflammatory and migratory cell response in the collected lymph between infected and non-infected as well as arthropod exposed and non-exposed animals. The project will also investigate if certain aspects of the innate and systemic immune response contribute to the development of disease in mammalian hosts, rather than conferring protection.
Initial studies will focus on the immune response of ruminants towards bluetongue virus infection and Culicoides spp. blood-feeding. Innate and systemic immune responses in ruminants towards Culicoides spp, can later be compared to responses of hosts towards other haematophagous arthropod vectors (e.g. ticks and mosquitoes) as well as additional arboviruses. The in-vitro work studying the immune response of skin cells and endothelial cells has the additional benefit of being transferable to include equine derived cells, therefore allowing research into important horse disease or in the wider future important zoonotic arboviruses such as West Nile virus.
Initial studies will focus on the immune response of ruminants towards bluetongue virus infection and Culicoides spp. blood-feeding. Innate and systemic immune responses in ruminants towards Culicoides spp, can later be compared to responses of hosts towards other haematophagous arthropod vectors (e.g. ticks and mosquitoes) as well as additional arboviruses. The in-vitro work studying the immune response of skin cells and endothelial cells has the additional benefit of being transferable to include equine derived cells, therefore allowing research into important horse disease or in the wider future important zoonotic arboviruses such as West Nile virus.
People |
ORCID iD |
| Karin Darpel (Principal Investigator) |
Publications
Batten C
(2014)
Evidence for transmission of bluetongue virus serotype 26 through direct contact.
in PloS one
Darpel KE
(2016)
Bluetongue - an ever present threat to UK ruminants?
in Cattle Practise
Darpel KE
(2016)
Using shared needles for subcutaneous inoculation can transmit bluetongue virus mechanically between ruminant hosts.
in Scientific reports
Rádrová J
(2016)
Hyaluronidase Activity in Saliva of European Culicoides (Diptera: Ceratopogonidae).
in Journal of medical entomology
Stevens Lisa M.
(2016)
Understanding the early events in Bluetongue virus cell entry
Stevens LM
(2019)
A low-passage insect-cell isolate of bluetongue virus uses a macropinocytosis-like entry pathway to infect natural target cells derived from the bovine host.
in The Journal of general virology
| Description | Additionally work funded by this award contributed to implementing a highly relevant in vivo animal study design where BTV is transmitted to the natural ruminant host via the blood-feeding of infected Culicoides biting midges. Combining infection studies in the natural host with insect transmission of the virus mimics natural arbovirus infection more closely and realistically than needle inoculations. An ELISA was developed to detect antibodies (immunoglobulins G, M and E) against Culicoides saliva proteins to analyse the immune response of cattle and horses to Culicoides blood-feeding. We have further analysed ruminant and horse serum by western blot to identify the specific immunogenic salivary proteins and while different serum anti-saliva IgG profiles are detectable certain proteins are dominantly recognised. The methodology of saliva collection was further transferred to Aedes aegypti mosquitoes - allowing to extend current research of the influence of arthropod vector saliva to mosquito-borne viruses. We previously demonstrated that saliva of the vector Culicoides sonorensis efficiently cleaves the outer coat protein of BTV, thereby changing its infectivity. In contrast Ae. aegypti saliva was not able to modify BTV proteins, suggesting that the interaction of vector saliva - arbovirus might reflect a selective relationship. Furthermore, we have established primary bovine cell culture models (monocytes, endothelial cells) as well as organ model ex vivo and demonstrated successful infection with BTV allowing the detection of BTV infected cells in model tissue sections as well as detection of progeny virus in organ culture supernatant. |
| Exploitation Route | The current studies investigating the effect of Culicoides saliva on co-transmitted viruses can also be transferred to research on other insect vector- arboviruses systems. Successfully transferring the methodology of saliva collection to Aedes mosquitoes will result in the availability of sufficient amounts of mosquito saliva for in-vitro studies on mosquito borne viruses. Furthermore being able to carry out in vivo studies using the natural host, vectors and virus complexes will provide a unique opportunity to compare results with those generated in models (mostly rodents) for animal and human arthropod-borne pathogen research. Other international research team have already implemented bluetongue virus pathogenesis studies in the context of Culicoides blood-feeding exposure to assess the impact on BTV virulence and infectivity |
| Sectors | Agriculture, Food and Drink |
| Description | Findings that some BTV strains ( such as BTV-26) can be transmitted by contact and others by oral and mechanical transmission routes will influence BTV control strategies, inform veterinary practitioners and impact on the design of BTV surveillance and diagnostic strategies |
| First Year Of Impact | 2014 |
| Sector | Agriculture, Food and Drink |
| Impact Types | Economic |
| Description | Bluetongue virus information campaign (JAB campaign led by National farmers Union) |
| Geographic Reach | Local/Municipal/Regional |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | The "Joint action against bluetongue" campaign of the National Farmers Union provided Veterinarians and Farmers with the opportunity to make an informed decision on BTV vaccination in accordance with the latest research following the re-emergence of BTV-8 in France and the subsequent availability of commercial BTV-8 vaccine. Preventing a Bluetongue virus outbreak in the UK will greatly benefit the national agriculture sector |
| Description | BBSRC The Pirbright Institute PhD studentship |
| Amount | £48,000 (GBP) |
| Funding ID | BBS/E/I/00001728 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 10/2013 |
| End | 09/2017 |
| Description | BBSRC responsive mode grant |
| Amount | £367,000 (GBP) |
| Funding ID | BB/P006841/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 10/2017 |
| End | 03/2019 |
| Description | Workpackage within a Horzion 20:20 grant |
| Amount | € 6,000,000 (EUR) |
| Funding ID | EU project 727393 Horizon 20:20 PALE-Blue |
| Organisation | European Union |
| Sector | Public |
| Country | European Union (EU) |
| Start | 07/2017 |
| End | 07/2021 |
| Description | Collaboration studentship BTV |
| Organisation | University of Surrey |
| Department | Faculty of Health and Medical Sciences |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Collaborative studentship with virologist at the University of Surrey, student registered at the University |
| Collaborator Contribution | Intellectual input, training of student |
| Impact | Thesis http://epubs.surrey.ac.uk/845643/ |
| Start Year | 2013 |
| Description | Collaborative studentship PPRV |
| Organisation | University of Surrey |
| Department | School of Veterinary Medicine |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Practical laboratory work and in vivo animal studies carried out |
| Collaborator Contribution | Intellectual input in scientific remit of studentship, training of student, use of facilities and lab |
| Impact | DOI: 10.1128/JVI.01471-18 Thesis: The immune response to live, attenuated peste des petits ruminants virus vaccines |
| Start Year | 2014 |
| Description | Microbial products in insect saliva and effects on virus infection enhancement |
| Organisation | Boston University School of Medicine |
| PI Contribution | Sharing of results on the discovery of bacterial LPS in Culicoides saliva and its infection enhancing effect on BTV in bovine monocytes. Discussion of future work and comparison of the results to other insect transmitted viruses including those of high importance to humans |
| Collaborator Contribution | Sharing of data from their portfolio on mosquito saliva effects on virus infectivity and replication. Comparison of methodology and discussion of future collaborations |
| Impact | On-going sharing of results and discussion of future experiments |
| Start Year | 2018 |
| Description | Pathology of bovine skin post Culicoides midge blood-feeding |
| Organisation | University of Surrey |
| Department | School of Veterinary Medicine |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Collection of skin samples from cattle responding with local inflammation to Culicoides biting midges blood feeding, sending of materials |
| Collaborator Contribution | Processing of samples, histopathological analysis, sharing of results |
| Impact | Further identification of cellular and histological local changes in ruminant skin to Culicoides blood-feeing which will inform pathogenesis of co-transmitted arboviruses such as BTV |
| Start Year | 2017 |
| Description | Attandence of the BBSRC cross institute microbiome workshop (7th and 8th January 2019) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Attendance of the BBSRC cross institute microbiome workshop (7th and 8th January 2019) by postdoctoral scientist - discussion of future collaborations and links |
| Year(s) Of Engagement Activity | 2019 |
| Description | Hampshire sheep discussion forum |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Industry/Business |
| Results and Impact | Presented and then led a discussion group on bluetongue virus emergence, current research and potential control measures to farmers, veterinarians and interested member of the public |
| Year(s) Of Engagement Activity | 2016 |
| Description | Invited speaker VECTOR-BORNE DISEASES (VBD) IN THE UK - BIENNIAL MEETING 2018 John Innes Centre Norwich |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited speaker on "The Host-vector-pathogen Interface of Culicoides-borne Bluetongue Virus" at the VECTOR-BORNE DISEASES (VBD) IN THE UK - BIENNIAL MEETING 2018 John Innes Centre Norwich 4th-5th December 2018 |
| Year(s) Of Engagement Activity | 2018 |
| Description | Presentation of project results at the 13th International dsRNA Virus Symposium 24th-28th of September 2018 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Poster and Oral presentations included key results of the studentship project |
| Year(s) Of Engagement Activity | 2018 |
| Description | Video podcast Understanding Animal Research |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Participated in filming and interviewing for a labanimaltour where 4 Research Institutes openly discuss the use of animals in research. Currently already more than 1000 views of the Bluetongue virus related video either on youtube or facebook |
| Year(s) Of Engagement Activity | 2016,2017 |
| URL | http://www.labanimaltour.org |
| Description | Video potcasts on youtube for BTV clinical signs |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Produced a youtube video on the clinical signs of bluetongue virus (an arbovirus of ruminants) together with colleagues from The Pirbright Institute and Animal and Plant Health Agency 3000 views so far |
| Year(s) Of Engagement Activity | 2016 |
| URL | https://www.youtube.com/watch?v=fwJ8zAxiLOE |