ANIHWA call 3: ARBONET Epidemiological models for control of arboviral disease for Europe
Lead Research Organisation:
University of Liverpool
Department Name: Institute of Infection and Global Health
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.
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.
- 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.
Organisations
- University of Liverpool (Lead Research Organisation)
- Animal and Plant Health Agency (Collaboration)
- Government of Sweden (Collaboration)
- UNIVERSITY OF NOTTINGHAM (Collaboration)
- Karolinska Institute (Collaboration)
- French Agency for Food, Environmental and Occupational Health & Safety (ANSES) (Collaboration)
- National Veterinary Institute (Collaboration)
- THE PIRBRIGHT INSTITUTE (Collaboration)
Publications
Al-Khafaji AM
(2020)
Isolation of Candidatus Rickettsia vini from Belgian Ixodes arboricola ticks and propagation in tick cell lines.
in Ticks and tick-borne diseases
Luu L
(2020)
Isolation and partial characterisation of a novel Trypanosoma from the tick Ixodes ricinus.
in Ticks and tick-borne diseases
Luu L
(2021)
Bacterial Pathogens and Symbionts Harboured by Ixodes ricinus Ticks Parasitising Red Squirrels in the United Kingdom.
in Pathogens (Basel, Switzerland)
Salata C
(2018)
The DEVD motif of Crimean-Congo hemorrhagic fever virus nucleoprotein is essential for viral replication in tick cells.
in Emerging microbes & infections
Salata C
(2020)
Identification and validation of internal reference genes for real-time quantitative polymerase chain reaction-based studies in Hyalomma anatolicum ticks.
in Ticks and tick-borne diseases
Salvati MV
(2021)
Virus-Derived DNA Forms Mediate the Persistent Infection of Tick Cells by Hazara Virus and Crimean-Congo Hemorrhagic Fever Virus.
in Journal of virology
Description | Crimean-Congo hemorrhagic fever virus (CCHFV) and Rift Valley fever virus (RVFV) both cause severe human disease and must be handled under high containment. Both are zoonoses transmitted by arthropods, respectively ticks and mosquitoes; research to understand the mechanisms of virus replication and persistence in the vectors, and transmission to vertebrate hosts, must also be carried out under high containment. Such work is very expensive and technically challenging. Arthropod cell lines provide model systems to study these viruses in a controlled and technically simpler manner. In this project we developed protocols for propagation of Hazara virus (a less-pathogenic relative of CCHFV that can be handled at biosafety level 2) and RVFV in tick and mosquito cell lines, and downstream analysis of gene transcription and protein expression. These protocols will be valuable for scientists studying these and other similar highly pathogenic arboviruses, enabling better understanding of how the viruses persist in nature and what factors affect their transmission from domestic and wild animals to humans. |
Exploitation Route | The protocols developed 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 will be applicable to further studies not only on CCHFV and RVFV, but also on other tick- and mosquito-borne arboviruses that cause disease in livestock and humans. Such studies will assist the search for improved vaccines and vector control methods. |
Sectors | Agriculture Food and Drink |
Title | Tick cell line HLE/LULS42 |
Description | Cell line derived from embryos of the tick Hyalomma lusitanicum from Spain, currently at passage 4 after 5 years in vitro |
Type Of Material | Cell line |
Year Produced | 2019 |
Provided To Others? | Yes |
Impact | This is the first cell line to be developed from Hyalomma lusitanicum, an important tick in Spain and the first tick species to be found to harbour the human pathogen Crimean-Congo hemorrhagic fever virus in Spain. |
Title | Tick cell line HLE/LULS43 |
Description | Continuous cell line derived from embryos of the tick Hyalomma lusitanicum, currently at passage 8 after six years in culture |
Type Of Material | Cell line |
Year Produced | 2019 |
Provided To Others? | Yes |
Impact | This is the second cell line to be established from the Spanish tick species Hyalomma lusitanicum, a potential vector of Crimean-Congo haemorrhagic fever. |
Title | Mosquito cell/RVFV transcriptomes |
Description | ARBONET team members University of Nottingham, APHA and The Pirbright Institute are generating transcriptomes of uninfected and Rift Valley fever virus-infected mosquito cell lines to identify genes differentially-transcribed upon virus infection. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | No |
Impact | None so far |
Title | Tick cell/HAZV transcriptomes and proteomes |
Description | We are generating transcriptomes and proteomes of tick cell lines infected with Hazara virus, a BSL2 model for Crimean-Congo hemorrhagic fever virus to determine genes and proteins differentially expressed upon virus infection. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | No |
Impact | None to date |
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 |
Description | Meet the Scientists |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Organised by the University of Liverpool's Faculty of Health and Life Sciences and supported by the Wellcome Trust, the programme aims to share the global impact of Liverpool research through fun and engaging activities and demonstrations. Staff and students from the Institute of Infection and Global Health hosted the first event on 24th November 2018 at Liverpool's World Museum. The theme was "Bacteria. Viruses. Parasites. They're everywhere. Come along and learn about all things infectious, how these organisms spread, and how we can prevent them spreading". Project staff manned stalls on parasites (including ticks) and biomarkers of infection, and interacted with members of the public of all ages from toddlers to grandparents. |
Year(s) Of Engagement Activity | 2018,2019 |
URL | https://news.liverpool.ac.uk/2018/11/23/new-series-of-meet-the-scientists-begins-this-weekend/ |