African swine fever virus genes involved in modifying virulence and host responses

Lead Research Organisation: The Pirbright Institute
Department Name: UNLISTED

Abstract

African swine fever virus (ASFV) is a large cytoplasmic double-stranded DNA virus, which encodes many proteins that are not essential for ASFV replication in cells, but have important roles in virus survival and transmission in its hosts, including those which help it evade the host’s innate and adaptive immune responses. ASFV causes a haemorrhagic fever in domestic pigs and can result in very high mortality leadimg to severe socio-economic impact. There is no vaccine and this limits options for disease control. A better understanding of how ASFV manipulates the host response to infection will underpin the development of effective vaccines. In this project we will continue to identify and investigate the function of ASFV proteins involved in virulence and in modulating host responses to infection. Key proteins, such as the protein phosphatase 1 regulator DP71L, already known to have roles in these processes will be further investigated. We have already shown DP71L inhibits stress-induced shut-off of global protein synthesis and we will investigate the hypothesis that DP71L has additional roles mediated through targeting PP1 to specific substrates. The ASFV transmembrane protein, CD2v, is required to facilitate virus dissemination in pigs and to impair the ability of lymphocytes to proliferate. The presence of the CD2v gene also enhances virus replication in the tick vector Ornithodoros at the level of virus uptake in the tick gut. We will identify cellular ligands for CD2v and define key functional domains. Novel proteins involved in modulating host responses and other functions will be identified using an ASFV expression library. The effect of deleting these and other genes from the ASFV genome will be investigated. Virus replication and host responses will be studied in macrophage cultures and in immunisation and challenge experiments in pigs to establish candidate attenuated vaccine strains.
 
Description The research has been used to develop candidate African swine fever virus live attenuated vaccine strains
First Year Of Impact 2012
Sector Agriculture, Food and Drink
Impact Types Economic

 
Description IAEA Advisor on African swine fever Coordinated Action Programme
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact I was an invited expert for an International Atomic Energy Association Coordinated Action Programme involving many African countries.
 
Description OIE World Animal Health Organisation, Designated Disease Expert on African swine fever
Geographic Reach Multiple continents/international 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
Impact Involved in giving advice to OIE and completion of chapters in OIE Guidelines for Diagnosis of African swine fever and Trade regulations.
URL http://www.oie.int/
 
Description Science Director Global Alliance for African swine fever virus research
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact I was Science Director of the Global Alliance for Research on African swine fever virus (GARA). This involved being Chair of the Scientific Organizing Committee for 2 International Meetings and preparing reports and GAP analysis to direct research.
URL https://www.ars.usda.gov/GARA/
 
Description UK national Expert on African swine fever
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
Impact Updates to DEFRA Risk Assessments on Exotic Diseases. Advice on particular queries from DEFRA
 
Description GALVmed DFID Funding
Amount £216,000 (GBP)
Organisation GALVmed 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2016 
End 09/2017
 
Description Zoetis Research Funding
Amount £550,000 (GBP)
Organisation Zoetis 
Sector Private
Country United States
Start 04/2017 
End 10/2018
 
Description Collaboration ILRI Kenya 
Organisation International Livestock Research Institute (ILRI)
Country Kenya 
Sector Charity/Non Profit 
PI Contribution Expertise on ASFV
Collaborator Contribution Expertise on ASFV in Africa, Access to warthogs/bushpigs
Impact Secondment to ILRI Kenya
Start Year 2014
 
Description Collaboration on ASFV immune evasion genes 
Organisation Gulbenkian Institute of Science
Country Portugal 
Sector Academic/University 
PI Contribution Assays of ASFV immune evasion genes in macrophages.
Collaborator Contribution Information of ASFV immune evasion genes from Dr Mike Parkhouse
Impact Multi-disciplinary involving molecular and cell biology and virology. 1 publication
Start Year 2007
 
Description Collaboration on ASFV inhibitors of IFN and stress responses 
Organisation St George's University of London
Country United Kingdom 
Sector Academic/University 
PI Contribution We made constructs to test ASFV genes that inhibit IFN and stress responses and tested these in cellular assays.
Collaborator Contribution Our partner Prof Steve Goodbourn provided advice and reagents for these assays and carried out some of the tests.
Impact 2 joint publications and supervision of a PhD student Claire Barber
Start Year 2007
 
Description Collaboration on ASFV transmission and epidemiology 
Organisation Royal Veterinary College (RVC)
Department Structure and Motion Laboratory
Country United Kingdom 
Sector Academic/University 
PI Contribution Animal experiments on the transmission mechanisms of ASFV
Collaborator Contribution Expertise in mathematical modelling and epidemiology
Impact Joint publications and Grant Applications
Start Year 2012
 
Description Collaboration on Structural Biology of African swine fever virus apoptosis inhibitors 
Organisation La Trobe University
Country Australia 
Sector Academic/University 
PI Contribution My research team provided expertise on African swine fever virus and identified host proteins that interact with virus inhibitors of apoptosis
Collaborator Contribution My partners (Drs Marc Kvansakul and Hinds La Trobe, Melbourne) determined the X-ray crystal structure of the African swine fever apoptosis inhibitor A179L and its binding affinity with interacting BH3 domain containing proteins
Impact Publication in J Virology. Grant Applications to Australian Research Council. Structural Biology, Virology, Cell Biology
Start Year 2014
 
Title Gene-deleted live attenuated African swine fever vaccine candidate 
Description We identified African swine fever virus genes that inhibit the host interferon antiviral response and showed that deletion of these from the virus genome attenuates the virus and can lead to induction of protection against challenge. Thus we identified a route to construct candidate live attenuated vaccines. 
IP Reference WO2015193685 
Protection Patent application published
Year Protection Granted 2015
Licensed No
Impact We have initiated a collaboration with Zoetis and GALVmed which has brought new funding to the project.
 
Description Advice to Visiting Scientist from Taiwain 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Visit from a scientist at The Central Veterinary Institute Taiwan for advice about diagnosis of African swine fever virus infection. Followed by a request for further information and reagents.
Year(s) Of Engagement Activity 2016
 
Description Agritech Forum Kiev Ukraine 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact I was invited by the UK Department of Trade and Industry to attend an Agritech Business Forum in Kiev Ukraine. I gave a presentation at a workshiop they organised and met with Ukrainian businesses, Vets, Policy makers and Farmers
Year(s) Of Engagement Activity 2016
 
Description Communication on Understanding Animal Research 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact I gave a presentation and discussed with students at Woking College my work and more generally in use of animals in research.
Year(s) Of Engagement Activity 2017
 
Description Expert Advice to Scientist from QIA Institute S Korea 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Training in laboratory methods for ASFV diagnosis. Testing of diagnostic kit
Year(s) Of Engagement Activity 2015
 
Description Expert Advisor International Atomic Energy Association 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited expert for IAEA Combined Action Programme on African swine fevef
Year(s) Of Engagement Activity 2016
 
Description Invited Presenattion ASF-STOP COST Action Pulawy Poland 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Two invited presentations at ASF-STOP kick-off meeting Pulawy Poland
Year(s) Of Engagement Activity 2016
 
Description Invited Presentation Plum Island Animal Disease Centre 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact An invited presentation on ASFV at the GARA Kick-Off meeting at Plum Island Animal Disease Centre USA
Year(s) Of Engagement Activity 2013
 
Description Invited Seminar AFBI Belfast 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited seminar and discussions AFBI Belfast
Year(s) Of Engagement Activity 2016
 
Description Invited Seminar China Animal Health and Epidemiology Centre Qingdao PR China 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited seminar at China Animal Health and Epidemiology Centre Qingdao PR China
Year(s) Of Engagement Activity 2012
 
Description Invited Seminar Friedraich Loeffler Institute 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited seminar on ASFV at FLI Institute Germany
Year(s) Of Engagement Activity 2013
 
Description Invited Seminar Liverpool University centre for Infectious Diseases (Skype to ILRI Kenya) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited seminar and discussions Liverspool University. Skype Link with ILRI Kenya
Year(s) Of Engagement Activity 2017
 
Description Invited Seminar University of Illinois 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited seminar University of Illinois Veterinary Faculty
Year(s) Of Engagement Activity 2012
 
Description Invited Seminar University of Utrecht 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited seminar on ASFV
Year(s) Of Engagement Activity 2013
 
Description Invited Talk ASFV symposium Kansas State University 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk at Symposium on ASFV Kansas State University
Year(s) Of Engagement Activity 2012
 
Description Invited expert International Atomic Energy Assocaition 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I was an invited expert on an IAEA panel to provide advice about a Combined Action Programme on ASFV
Year(s) Of Engagement Activity 2013
 
Description Invited seminar Yangzhou University PR China 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Presentation to postgraduate students and faculty at Yangxhou University Veterinary faculty
Year(s) Of Engagement Activity 2012
 
Description Invited seminar at QIA Institute S Korea 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited seminar and discussions about African swine fever at QIA Institute S Korea
Year(s) Of Engagement Activity 2014
 
Description Invited talk Ames Iowa USA. Vaccines and Diagnostics for Transboundary Animal Diseases 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited Keynote Talk at International Symposium on Vaccines and Diagnostics for Transboundary Animal Diseases., Ames Iowa
Year(s) Of Engagement Activity 2012
 
Description Member of Expert Group on Roadmap and Blueprint for an African swine fever vrius vaccine 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact I was a member of an EU commissioned working group on preparation of a Roadmap and Blueprint for an African swine fever virus vaccine. The group comprised ~ 15 experts. One 2 day face to face meeting, a telephone conference were held in addition to preparation of a 36 page report.
The aim of the ASF blueprint and roadmap is to give an overview of the research efforts needed and help to direct investments towards specific areas.

The STRATEGIC GOALS identified include:
•Identification of potential strategies for vaccine development based on existing data/knowledge in a view of an effective and safe vaccine.
•Identification of gaps and needs for vaccine development and manufacturing following the Good Manufacturing Practice Standards.
•Identification of a network of dedicated laboratories directed towards vaccine development
•Identification of the research steps (Roadmap)
The report has been published on the EU website http://ec.europa.eu/food/sites/food/files/safety/docs/cff_animal_vet-progs_asf_blue-print-road-map.pdf
Year(s) Of Engagement Activity 2016,2017
URL http://ec.europa.eu/food/sites/food/files/safety/docs/cff_animal_vet-progs_asf_blue-print-road-map.p...
 
Description Organising Committee EPIZONE Annual Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I have been a member of the scientific organizing committee of the EU EPIZONE Network every year since its founding in 2005 except for 2015.
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010
URL http://www.epizone-eu.net
 
Description Organizing Committee Global African swine fever virus Research Alliance Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I was on the organizing committee of the GARA biannual meeting held in Ploufragan, France, September 2016. This involved inviting international speakers, organizing scientific sessions and chairing of sessions
Year(s) Of Engagement Activity 2016
URL https://www.ars.usda.gov/GARA/
 
Description Presentations to Epizootic Disease control groups in Scotland and N Ireland 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact I gave a presentation and was involved in discussions with scientists and policy makers involved in control of Epizootic Diseases. One talk was in Scotland and another in N Irelands
Year(s) Of Engagement Activity 2013
 
Description Representative at Pig and Poultry Fair, Stoneleigh UK 
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 I represented The Pirbright Institute at a Stand at the Pig and Poultry Fair, Stoneleigh Warwickshire and discussed with farmers, vets, policy makers, schools
Year(s) Of Engagement Activity 2016
 
Description Scientific Chair Vaccine Session Poxvirus, Asfarvirus, Iridovirus International Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I was chairperson of the scientific session on Vaccines at the International Poxvirus, Asfarvirus and Iridovirus Workshop held in Strasbourg France June 2016. I selected abstracts for oral and poster presentations and acted as chair during the session.
Year(s) Of Engagement Activity 2016
 
Description Talk at Korean Society for Veterinary Virology 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited Presentation on African swine fever at Korean Society for Veterinary Science
Year(s) Of Engagement Activity 2014
 
Description Visit to QIA Institute S Korea 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Visit to QIA Institute S Korea to provide expert advice on ASFV
Year(s) Of Engagement Activity 2013
 
Description Visiting Scientist from CReSA Barcelona 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact A postgraduate student from CReSA Barcelona visited for collaborative research and training for 6 months
Year(s) Of Engagement Activity 2016