ANIHWA call 3: ARBONET Epidemiological models for control of arboviral disease for Europe

Lead Research Organisation: The Pirbright Institute
Department Name: Vector-borne Viral Diseases

Abstract

Emerging and re-emerging infectious viral diseases continue to challenge both animal and human health around the world. For Europe, vector-borne infections, such as mosquito-borne West Nile fever (WNF), and Rift Valley fever (RVF) and tick-borne Crimean-Congo hemorrhagic fever (CCHF), pose a continuous risk of incursions or northward expansion from endemic areas. The drivers of these infections are multifactorial and include increased mobility of human populations, increased global trade in live animals and foodstuffs, and climate change affecting the geographic distribution and competence of vectors. In addition, persistent arbovirus infections in wildlife pose unprecedented challenges to formulation of proper surveillance and control actions, due to the complexity of the interfaces between different host populations.The proposed initiative "ARBONET" will be focused on WNF, CCHF and RVF infections, specifically on development of epidemiological models that can inform risk-based surveillance and interventions that can control disease outbreaks in Europe. The major goal of this joint initiative is to create a multidisciplinary research network combining the expertise of veterinary and human epidemiologists, disease modellers, virologists and arthropod biologists to increase knowledge and understanding that will facilitate rapid control of disease outbreaks. The ARBONET proposal has the following specific objectives: 1) to develop epidemiological models of possible scenarios of CCHF, RVF and WNF spread in Europe, evaluating possible risk-based surveillance approaches and control strategies, 2) to promote epidemiological studies on distribution of viral genetic subpopulations, 3) to increase the knowledge of virus-vector and virus-vertebrate host interactions, and 4) to support dissemination of knowledge on the epidemiology, surveillance and control of these diseases.

Technical Summary

In Europe, the vector-borne viruses West Nile virus (WNV), Rift Valley fever virus (RVFV) and Crimean-Congo hemorrhagic fever virus (CCHFV) pose a continuous risk of incursions or northward expansion from endemic areas. ARBONET will focus on development of epidemiological models to inform risk-based surveillance and interventions to control WNV, CCHFV and RVFV disease outbreaks in Europe. ARBONET's specific objectives are: 1) to develop epidemiological models of possible scenarios of CCHFV, RVFV and WNV spread in Europe, evaluating possible risk-based surveillance approaches and control strategies, 2) to promote epidemiological studies on distribution of viral genetic subpopulations, 3) to increase the knowledge of virus-vector and virus-vertebrate host interactions, and 4) to support dissemination of knowledge on the epidemiology, surveillance and control of these diseases.

Workpackage 5, led by The Pirbright Institute, will carry out appraisal of the main drivers of CCHFV, RVFV and WNV infections in arthropods, using published and new research on novel aspects of arthropod infections with these viruses to:
- Establish general platforms (data, protocols, methods and work streams) for in vitro studies on the up- and down-regulation of arthropod host cell genes in response to virus infection in tick and mosquito cell lines (small scale and high-throughput)
- Establish general platforms as above for in vivo studies on the up- and down-regulation of arthropod host cell genes in response to virus infection in ticks and mosquitoes
- Use the established platforms to generate transcriptomic, proteomic and interactomic datasets from uninfected and virus-infected tick and mosquito cell lines and whole arthropods to characterise the vector and non-vector cell response to arbovirus infection and thereby better understand the biology of the infection.
- Investigate the mutations in the WNV genome induced by single host (mosquito or vertebrate) adaptation.

Planned Impact

In addition to the academic beneficiaries listed in the previous section, the following groups should benefit from this research:

- Key policy makers dealing with European preparedness against incursion by vector-borne diseases who will have access to improved risk modelling and prediction tools based on a better understanding of the epidemiology of WNV, RVFV and CCHFV infections and the relationship between the viruses and their mosquito and tick vectors

- The general public, including UK and European clinicians, farmers and slaughterhouse workers, who will have access to improved, more accurate non-technical information on vector-borne diseases in general, and WNV, RVFV and CCHFV in a European context in particular, via the consortium website and press releases

Release of research results will be managed according to the general rules on dissemination of intellectual property in the consortium agreement. 'Foreground' is the results, information, materials and knowledge generated in the project, whether protectable or not. This includes intellectual property rights (IPR) and unprotected know-how (e.g. confidential material). The consortium is obliged to protect, use and disseminate foreground. Important components of IPR (e.g. confidentiality, joint ownership, transfer of foreground) and access rights will be specified in the Consortium Agreement. Participants planning dissemination must obtain approval from the consortium and deal with objections from participants who consider that some data need to be protected before dissemination. Foreground and competencies within the consortium will be disseminated by regular meetings of the consortium and participants of each workpackage whenever needed. Moreover, student and post-doc participants in the consortium will circulate between laboratories to improve the effectiveness of research. The capacity-building training course on epidemiology and surveillance, and the e-learning training course will also improve the effectiveness of dissemination. New knowledge generated by the project will be made available to the public according to the general rules on dissemination in the consortium agreement.

Publications

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Related Projects

Project Reference Relationship Related To Start End Award Value
BB/N023889/1 02/06/2016 31/03/2017 £235,880
BB/N023889/2 Transfer BB/N023889/1 01/04/2017 29/02/2020 £207,535
 
Description Crimean-Congo hemorrhagic fever virus (CCHFV) is transmitted by ticks of the genus Hyalomma, and causes severe, often fatal, hemorrhagic disease in humans bitten by infected ticks. CCHFV must be handled under high (Biosafety level 4) containment, and it is extremely difficult to carry out experiments with infected ticks under these conditions. Tick cell lines offer a more easily-handled alternative to live ticks. One of the aims of this project was to develop protocols for transcriptomic analysis of tick cell lines infected with CCHFV to investigate the interaction between the virus and the tick cells. ANIHWA colleagues at Karolinska Institute generated samples for RNA sequencing from CCHFV-infected Hyalomma cell lines. The bioinformatics analysis of this sequence data was carried out within this project and 40 candidate tick genes were identified as being differentially expressed between as a result of CCHFV infection. The analysis was complicated by not having a reference genome for Hyalomma ticks and there being no previous transcriptomics studies using this tick genus, and only 19 genes could be ascribed a known biological function. Despite these constraints, the bioinformatics analysis provides a useful baseline for further studies using Hyalomma cells and a BSL2 model virus, Hazara virus (HAZV).
Exploitation Route The findings will be taken forward at University of Liverpool via the transferred grant BB/N023889/2
Sectors Agriculture, Food and Drink,Healthcare,Leisure Activities, including Sports, Recreation and Tourism

 
Description ANIHWA 3rd Call (NB total award to consortium below is given in euros )
Amount £1,797,035 (GBP)
Funding ID BB/N023889/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 06/2016 
End 06/2019
 
Description Collaboration with ANSES Paris on tick-borne virus propagation in tick cell lines 
Organisation French Agency for Food, Environmental and Occupational Health & Safety (ANSES)
Country France 
Sector Public 
PI Contribution I have provided them with tick cell lines and associated training for use in the ARBONET project in which we are both partners
Collaborator Contribution They will share results with me from their experiments on propagation of West Nile virus in tick cell lines.
Impact No outcomes yet
Start Year 2016
 
Description Collaboration with APHA (AHVLA) on virus propagation 
Organisation Animal and Plant Health Agency
Country United Kingdom 
Sector Public 
PI Contribution I have provided APHA (previously AHVLA) with tick cell lines and training in their maintenance on several occasions since 2006
Collaborator Contribution Collaborators at AHPA used the tick cell lines for attempted propagation of bat lyssaviruses and successful propagation of louping ill virus
Impact Joint research publication Mansfield et al 2017 http://dx.doi.org/10.1186/s13071-017-2011-1 A joint funding proposal was submitted to the third ANIHWA call; this was awarded and started in 2016. The project, coordinated by Prof Ali Mirazimi, Karolinska Institute, includes AHPA and Pirbright; Dr Lesley Bell-Sakyi is the Pirbright PI.
Start Year 2006
 
Description Collaboration with Karolinska, SVA and Swedish Public Health Agency on CCHFV 
Organisation Government of Sweden
Department Swedish Institute for Infectious Disease Control
Country Sweden 
Sector Public 
PI Contribution I provided the collaborators with tick cell lines for propagation of Crimean-Congo hemorrhagic fever virus, and ongoing technical advice on their maintenance
Collaborator Contribution The collaborators used the tick cell lines to propagate CCHFV under BSL4 conditions, and a non-pathogenic relative Hazara virus under BSL2 conditions.
Impact A jointly co-authored poster "Nairoviruses chronically infected Hyalomma-derived cell lines" (Salato, C., Karlberg, H., Bell-Sakyi, L., Palu, G., Mirazimi, A.) was presented at the 5th European Virology Congress in Lyon in 2013. A joint funding proposal was submitted to the third ANIHWA call; this was awarded and started in 2016. The project is coordinated by Prof Ali Mirazimi, Karolinska Institute, and Dr Lesley Bell-Sakyi is the Pirbright PI.
Start Year 2012
 
Description Collaboration with Karolinska, SVA and Swedish Public Health Agency on CCHFV 
Organisation Karolinska Institute
Country Sweden 
Sector Academic/University 
PI Contribution I provided the collaborators with tick cell lines for propagation of Crimean-Congo hemorrhagic fever virus, and ongoing technical advice on their maintenance
Collaborator Contribution The collaborators used the tick cell lines to propagate CCHFV under BSL4 conditions, and a non-pathogenic relative Hazara virus under BSL2 conditions.
Impact A jointly co-authored poster "Nairoviruses chronically infected Hyalomma-derived cell lines" (Salato, C., Karlberg, H., Bell-Sakyi, L., Palu, G., Mirazimi, A.) was presented at the 5th European Virology Congress in Lyon in 2013. A joint funding proposal was submitted to the third ANIHWA call; this was awarded and started in 2016. The project is coordinated by Prof Ali Mirazimi, Karolinska Institute, and Dr Lesley Bell-Sakyi is the Pirbright PI.
Start Year 2012
 
Description Collaboration with Karolinska, SVA and Swedish Public Health Agency on CCHFV 
Organisation National Veterinary Institute
Country Sweden 
Sector Public 
PI Contribution I provided the collaborators with tick cell lines for propagation of Crimean-Congo hemorrhagic fever virus, and ongoing technical advice on their maintenance
Collaborator Contribution The collaborators used the tick cell lines to propagate CCHFV under BSL4 conditions, and a non-pathogenic relative Hazara virus under BSL2 conditions.
Impact A jointly co-authored poster "Nairoviruses chronically infected Hyalomma-derived cell lines" (Salato, C., Karlberg, H., Bell-Sakyi, L., Palu, G., Mirazimi, A.) was presented at the 5th European Virology Congress in Lyon in 2013. A joint funding proposal was submitted to the third ANIHWA call; this was awarded and started in 2016. The project is coordinated by Prof Ali Mirazimi, Karolinska Institute, and Dr Lesley Bell-Sakyi is the Pirbright PI.
Start Year 2012
 
Description Collaboration with The Pirbright Institute 
Organisation The Pirbright Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution We are providing RNA etxracted from arbovirus-infected tick cell lines for transcriptomic analysis as part of the ARBONET project I am generating a novel cell line from the UK midge Culicoides nubeculosus which will be shared with Pirbright as part of the EU-funded PALE-Blu project
Collaborator Contribution Pirbright are carrying out collaborative RNA sequencing and transcriptomic analysis of arbovirus-infected tick and mosquito cells as part of the ARBONET project. The Pirbright Insectary provided the Tick Cell Biobank with eggs from C. nubeculosus midges for cell line establishment.
Impact None so far
Start Year 2017
 
Description Collaboration with University of Nottingham 
Organisation University of Nottingham
Department School of Veterinary Medicine and Science Nottingham
Country United Kingdom 
Sector Academic/University 
PI Contribution I am generating novel cell lines from UK, European, African and Middle Eastern midge species as part of the EU-funded PALE-Blu consortium. This work is done under sub-contract to University of Nottingham.
Collaborator Contribution As part of the ARBONET project, a University of Nottingham staff member has provided training to my team in virus culture and monitoring, and is involved in transcriptomic analysis of arbovirus-mosquito interactions.
Impact None yet
Start Year 2017