Studentship: Inter-serotypic genetic evolution of Foot-and-Mouth Disease Virus
Lead Research Organisation:
THE PIRBRIGHT INSTITUTE
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
Studentship: Foot-and-mouth disease virus (FMDV) is very genetically diverse and exists as a swarm of genetically related variants. This enables the virus to adapt rapidly to new environments and evade immune responses. The genetic variants seen at a herd and global level are a direct result of the virus diversity that is created through spontaneous mutation and recombination at the cell level. Processes such as genetic drift, migration and selection act upon the genetic variants to result in the genetic phenotypes characterised. Thus transmission events, and host immune responses shape the genetic diversity that is produced by the virus. FMDV exists in seven different serotypes which differ in their epidemiology (transmission, virulence, immunogenicity) and herd level genetic diversity. However, it is not known whether these differences are governed by environment and host, or whether the viruses have modified their own replication and diversity generation to achieve survival in a specific ecological niche.
Understanding how viruses generate diversity is crucial to studying the spread of virus and controlling disease. This PhD project addresses the question as to whether the variation between evolutionary phenotypes of the seven serotypes of FMDV at an epidemiological level, are due to inherent differences in the amount and structure of genetic diversity generated at a cellular level. The project evaluates the impact of varying replicative rates, protein diversity and genetic sequence flexibility on the generation and maintenance of genetic diversity within virus populations. The work embraces a cross disciplinary research approach incorporating molecular biology, next generation sequencing, and mathematical modelling of data.
Understanding how viruses generate diversity is crucial to studying the spread of virus and controlling disease. This PhD project addresses the question as to whether the variation between evolutionary phenotypes of the seven serotypes of FMDV at an epidemiological level, are due to inherent differences in the amount and structure of genetic diversity generated at a cellular level. The project evaluates the impact of varying replicative rates, protein diversity and genetic sequence flexibility on the generation and maintenance of genetic diversity within virus populations. The work embraces a cross disciplinary research approach incorporating molecular biology, next generation sequencing, and mathematical modelling of data.
Planned Impact
unavailable
Organisations
- THE PIRBRIGHT INSTITUTE (Lead Research Organisation)
- FGBI Federal Centre for Animal Health (Collaboration)
- French Agency for Food, Environmental and Occupational Health & Safety (ANSES) (Collaboration)
- Lombardy and Emilia Romagna Experimental Zootechnic Institute (IZSLER) (Collaboration)
- National Agri-Food Quality and Health Service (SENASA) (Collaboration)
- Onderstepoort Veterinary Institute (Collaboration)
- Project Directorate on Foot and Mouth Disease (Collaboration)
- Lanzhou Veterinary Research Institute (Collaboration)
- Botswana Vaccine Institute (Collaboration)
- Department of Livestock Development (Collaboration)
- U.S. Department of Agriculture USDA (Collaboration)
- UNIVERSITY OF GLASGOW (Collaboration)
- Veterinary and Agrochemical Research Centre (Collaboration)
- National Centre for Foreign Animal Diseases (NCFAD) (Collaboration)
- Pan American Foot-and-Mouth Disease Center (Panaftosa) (Collaboration)
People |
ORCID iD |
| Donald King (Principal Investigator) | |
| Eleanor Cottam (Co-Investigator) |
Publications
Ferretti L
(2018)
Within-Host Recombination in the Foot-and-Mouth Disease Virus Genome.
in Viruses
Logan G
(2018)
Deep Sequencing of Foot-and-Mouth Disease Virus Reveals RNA Sequences Involved in Genome Packaging.
in Journal of virology
Logan G
(2018)
Deep Sequencing of Foot-and-Mouth Disease Virus Reveals RNA Sequences Involved in Genome Packaging.
in Journal of virology
| Description | Foot-and-mouth disease virus (FMDV) (Family: Picornaviridae, Genus: Aphthovirus) is a significant global pathogen with extensive economic impacts. It is an RNA virus that contains a low fidelity RNA-dependent RNA polymerase and lacks proof reading capability. This coupled with its relatively short generation time and large population sizes means that it exists in a swarm of genetically closely related variants. The reservoir of diversity contained within this mutant spectrum allows the virus to adapt rapidly to new environments. Much of the previous work looking at virus evolution has focused on the consensus level genetic sequence. The advent of next generation sequencing (NGS) technologies enables evolutionary studies of the entire viral swarm. This PhD project used NGS technologies to interrogate the swarm structure by investigating factors affecting the viral swarm and the dynamics of variants within it. Furthermore, this work showed how analysis of the swarm can reveal fundamental information about the virus itself. Work was completed to establish a PCR-free NGS methodology to create deep sequencing data sets of all genomes present within an FMDV viral swarm. The elimination of the PCR step results in less errors being introduced in the sequencing process thereby improving the resolution and reliability of the identification of low level variants within the swarm. This optimised method was then used to define and compare the FMDV swarms of several wildtype isolates. This revealed differences in swarm structure from isolate to isolate and produced evidence of within swarm selection, different from selection at the consensus level. In some instances these difference were found to be due to the host from which a virus was sampled with African buffalo potentially able to maintain multiple infections. Subconsensus variants in these mixed samples had mutations at positions previously associated with immune escape. An experiment to observe how the swarm structure evolves was undertaken and results suggested two distinct populations structures with different distributions of variable nucleotide positions (when under adaptive pressure or not) but with comparative total levels of variation (as measured by Shannon's entropy). Finally this work considered how this understanding of the swarm can be used in fundamental virological studies using picornavirus packaging as an example. These experiments identified conserved novel stem loop structures that when mutated produced a virus which appeared to have a decreased packaging efficiency. |
| Exploitation Route | This thesis includes novel analysis techniques for considering the viral swarm. It demonstrates how investigating the diversity in the swarm can help to understand how a virus will evolve and the limits on this. Understanding viral evolution at this scale has the capacity to improve our fundamental understanding of the evolution of FMDV which can in turn inform vaccine design and disease control strategies. |
| Sectors | Agriculture Food and Drink Education Environment Pharmaceuticals and Medical Biotechnology |
| Title | Deep sequencing to identify RNA packaging signals |
| Description | A novel and simple approach to identify predicted RNA secondary structures involved in genome packaging in positive sense RNA viruses (e.g. the picornavirus foot-and-mouth disease virus [FMDV]). By interrogating deep sequencing data generated from both packaged and unpackaged populations of RNA, we have determined multiple regions of the genome with constrained variation in the packaged population. Predicted secondary structures of these regions revealed stem-loops with conservation of structure and a common motif at the loop. Disruption of these features resulted in attenuation of virus growth in cell culture due to a reduction in assembly of mature virions. This study provides evidence for the involvement of predicted RNA structures in picornavirus packaging and offers a readily transferable methodology for identifying packaging requirements in many other viruses. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2017 |
| Provided To Others? | Yes |
| Impact | Impact so far is fundamental knowledge but with several potential avenues for future impact in for example improved vaccines. |
| Description | OIE/FAO Laboratory Network for FMD |
| Organisation | Botswana Vaccine Institute |
| Country | Botswana |
| Sector | Public |
| PI Contribution | The Pirbright Institute currently coordinates a global network of fourteen International Reference Laboratories for FMD. |
| Collaborator Contribution | The Network of OIE/FAO FMD Reference Laboratories has been established with two principal goals: 1) To understand global virus distribution patterns and use these data to inform vaccine recommendations and 2) To harmonise and improve the quality of laboratory testing carried out by international and national reference laboratories. These activities require sharing and joint evaluation of surveillance information from laboratory diagnosis, serotyping, genetic characterisation and vaccine matching tests and harmonisation of standards for diagnostic procedures. |
| Impact | Outputs from the network provide vital information to international organisations involved in the control of FMD (such as OIE and FAO), as well as specific regional and national programmes to control FMD |
| Start Year | 2006 |
| Description | OIE/FAO Laboratory Network for FMD |
| Organisation | Department of Livestock Development |
| Country | Thailand |
| Sector | Public |
| PI Contribution | The Pirbright Institute currently coordinates a global network of fourteen International Reference Laboratories for FMD. |
| Collaborator Contribution | The Network of OIE/FAO FMD Reference Laboratories has been established with two principal goals: 1) To understand global virus distribution patterns and use these data to inform vaccine recommendations and 2) To harmonise and improve the quality of laboratory testing carried out by international and national reference laboratories. These activities require sharing and joint evaluation of surveillance information from laboratory diagnosis, serotyping, genetic characterisation and vaccine matching tests and harmonisation of standards for diagnostic procedures. |
| Impact | Outputs from the network provide vital information to international organisations involved in the control of FMD (such as OIE and FAO), as well as specific regional and national programmes to control FMD |
| Start Year | 2006 |
| Description | OIE/FAO Laboratory Network for FMD |
| Organisation | FGBI Federal Centre for Animal Health |
| Country | Russian Federation |
| Sector | Public |
| PI Contribution | The Pirbright Institute currently coordinates a global network of fourteen International Reference Laboratories for FMD. |
| Collaborator Contribution | The Network of OIE/FAO FMD Reference Laboratories has been established with two principal goals: 1) To understand global virus distribution patterns and use these data to inform vaccine recommendations and 2) To harmonise and improve the quality of laboratory testing carried out by international and national reference laboratories. These activities require sharing and joint evaluation of surveillance information from laboratory diagnosis, serotyping, genetic characterisation and vaccine matching tests and harmonisation of standards for diagnostic procedures. |
| Impact | Outputs from the network provide vital information to international organisations involved in the control of FMD (such as OIE and FAO), as well as specific regional and national programmes to control FMD |
| Start Year | 2006 |
| Description | OIE/FAO Laboratory Network for FMD |
| Organisation | French Agency for Food, Environmental and Occupational Health & Safety (ANSES) |
| Country | France |
| Sector | Public |
| PI Contribution | The Pirbright Institute currently coordinates a global network of fourteen International Reference Laboratories for FMD. |
| Collaborator Contribution | The Network of OIE/FAO FMD Reference Laboratories has been established with two principal goals: 1) To understand global virus distribution patterns and use these data to inform vaccine recommendations and 2) To harmonise and improve the quality of laboratory testing carried out by international and national reference laboratories. These activities require sharing and joint evaluation of surveillance information from laboratory diagnosis, serotyping, genetic characterisation and vaccine matching tests and harmonisation of standards for diagnostic procedures. |
| Impact | Outputs from the network provide vital information to international organisations involved in the control of FMD (such as OIE and FAO), as well as specific regional and national programmes to control FMD |
| Start Year | 2006 |
| Description | OIE/FAO Laboratory Network for FMD |
| Organisation | Lanzhou Veterinary Research Institute |
| Country | China |
| Sector | Learned Society |
| PI Contribution | The Pirbright Institute currently coordinates a global network of fourteen International Reference Laboratories for FMD. |
| Collaborator Contribution | The Network of OIE/FAO FMD Reference Laboratories has been established with two principal goals: 1) To understand global virus distribution patterns and use these data to inform vaccine recommendations and 2) To harmonise and improve the quality of laboratory testing carried out by international and national reference laboratories. These activities require sharing and joint evaluation of surveillance information from laboratory diagnosis, serotyping, genetic characterisation and vaccine matching tests and harmonisation of standards for diagnostic procedures. |
| Impact | Outputs from the network provide vital information to international organisations involved in the control of FMD (such as OIE and FAO), as well as specific regional and national programmes to control FMD |
| Start Year | 2006 |
| Description | OIE/FAO Laboratory Network for FMD |
| Organisation | Lombardy and Emilia Romagna Experimental Zootechnic Institute (IZSLER) |
| Country | Italy |
| Sector | Public |
| PI Contribution | The Pirbright Institute currently coordinates a global network of fourteen International Reference Laboratories for FMD. |
| Collaborator Contribution | The Network of OIE/FAO FMD Reference Laboratories has been established with two principal goals: 1) To understand global virus distribution patterns and use these data to inform vaccine recommendations and 2) To harmonise and improve the quality of laboratory testing carried out by international and national reference laboratories. These activities require sharing and joint evaluation of surveillance information from laboratory diagnosis, serotyping, genetic characterisation and vaccine matching tests and harmonisation of standards for diagnostic procedures. |
| Impact | Outputs from the network provide vital information to international organisations involved in the control of FMD (such as OIE and FAO), as well as specific regional and national programmes to control FMD |
| Start Year | 2006 |
| Description | OIE/FAO Laboratory Network for FMD |
| Organisation | National Agri-Food Quality and Health Service (SENASA) |
| Country | Argentina |
| Sector | Public |
| PI Contribution | The Pirbright Institute currently coordinates a global network of fourteen International Reference Laboratories for FMD. |
| Collaborator Contribution | The Network of OIE/FAO FMD Reference Laboratories has been established with two principal goals: 1) To understand global virus distribution patterns and use these data to inform vaccine recommendations and 2) To harmonise and improve the quality of laboratory testing carried out by international and national reference laboratories. These activities require sharing and joint evaluation of surveillance information from laboratory diagnosis, serotyping, genetic characterisation and vaccine matching tests and harmonisation of standards for diagnostic procedures. |
| Impact | Outputs from the network provide vital information to international organisations involved in the control of FMD (such as OIE and FAO), as well as specific regional and national programmes to control FMD |
| Start Year | 2006 |
| Description | OIE/FAO Laboratory Network for FMD |
| Organisation | National Centre for Foreign Animal Diseases (NCFAD) |
| Country | Canada |
| Sector | Public |
| PI Contribution | The Pirbright Institute currently coordinates a global network of fourteen International Reference Laboratories for FMD. |
| Collaborator Contribution | The Network of OIE/FAO FMD Reference Laboratories has been established with two principal goals: 1) To understand global virus distribution patterns and use these data to inform vaccine recommendations and 2) To harmonise and improve the quality of laboratory testing carried out by international and national reference laboratories. These activities require sharing and joint evaluation of surveillance information from laboratory diagnosis, serotyping, genetic characterisation and vaccine matching tests and harmonisation of standards for diagnostic procedures. |
| Impact | Outputs from the network provide vital information to international organisations involved in the control of FMD (such as OIE and FAO), as well as specific regional and national programmes to control FMD |
| Start Year | 2006 |
| Description | OIE/FAO Laboratory Network for FMD |
| Organisation | Onderstepoort Veterinary Institute |
| Country | South Africa |
| Sector | Academic/University |
| PI Contribution | The Pirbright Institute currently coordinates a global network of fourteen International Reference Laboratories for FMD. |
| Collaborator Contribution | The Network of OIE/FAO FMD Reference Laboratories has been established with two principal goals: 1) To understand global virus distribution patterns and use these data to inform vaccine recommendations and 2) To harmonise and improve the quality of laboratory testing carried out by international and national reference laboratories. These activities require sharing and joint evaluation of surveillance information from laboratory diagnosis, serotyping, genetic characterisation and vaccine matching tests and harmonisation of standards for diagnostic procedures. |
| Impact | Outputs from the network provide vital information to international organisations involved in the control of FMD (such as OIE and FAO), as well as specific regional and national programmes to control FMD |
| Start Year | 2006 |
| Description | OIE/FAO Laboratory Network for FMD |
| Organisation | Pan American Foot-and-Mouth Disease Center (Panaftosa) |
| Country | Brazil |
| Sector | Charity/Non Profit |
| PI Contribution | The Pirbright Institute currently coordinates a global network of fourteen International Reference Laboratories for FMD. |
| Collaborator Contribution | The Network of OIE/FAO FMD Reference Laboratories has been established with two principal goals: 1) To understand global virus distribution patterns and use these data to inform vaccine recommendations and 2) To harmonise and improve the quality of laboratory testing carried out by international and national reference laboratories. These activities require sharing and joint evaluation of surveillance information from laboratory diagnosis, serotyping, genetic characterisation and vaccine matching tests and harmonisation of standards for diagnostic procedures. |
| Impact | Outputs from the network provide vital information to international organisations involved in the control of FMD (such as OIE and FAO), as well as specific regional and national programmes to control FMD |
| Start Year | 2006 |
| Description | OIE/FAO Laboratory Network for FMD |
| Organisation | Project Directorate on Foot and Mouth Disease |
| Country | India |
| Sector | Public |
| PI Contribution | The Pirbright Institute currently coordinates a global network of fourteen International Reference Laboratories for FMD. |
| Collaborator Contribution | The Network of OIE/FAO FMD Reference Laboratories has been established with two principal goals: 1) To understand global virus distribution patterns and use these data to inform vaccine recommendations and 2) To harmonise and improve the quality of laboratory testing carried out by international and national reference laboratories. These activities require sharing and joint evaluation of surveillance information from laboratory diagnosis, serotyping, genetic characterisation and vaccine matching tests and harmonisation of standards for diagnostic procedures. |
| Impact | Outputs from the network provide vital information to international organisations involved in the control of FMD (such as OIE and FAO), as well as specific regional and national programmes to control FMD |
| Start Year | 2006 |
| Description | OIE/FAO Laboratory Network for FMD |
| Organisation | U.S. Department of Agriculture USDA |
| Department | Agricultural Research Service |
| Country | United States |
| Sector | Public |
| PI Contribution | The Pirbright Institute currently coordinates a global network of fourteen International Reference Laboratories for FMD. |
| Collaborator Contribution | The Network of OIE/FAO FMD Reference Laboratories has been established with two principal goals: 1) To understand global virus distribution patterns and use these data to inform vaccine recommendations and 2) To harmonise and improve the quality of laboratory testing carried out by international and national reference laboratories. These activities require sharing and joint evaluation of surveillance information from laboratory diagnosis, serotyping, genetic characterisation and vaccine matching tests and harmonisation of standards for diagnostic procedures. |
| Impact | Outputs from the network provide vital information to international organisations involved in the control of FMD (such as OIE and FAO), as well as specific regional and national programmes to control FMD |
| Start Year | 2006 |
| Description | OIE/FAO Laboratory Network for FMD |
| Organisation | Veterinary and Agrochemical Research Centre |
| Country | Belgium |
| Sector | Public |
| PI Contribution | The Pirbright Institute currently coordinates a global network of fourteen International Reference Laboratories for FMD. |
| Collaborator Contribution | The Network of OIE/FAO FMD Reference Laboratories has been established with two principal goals: 1) To understand global virus distribution patterns and use these data to inform vaccine recommendations and 2) To harmonise and improve the quality of laboratory testing carried out by international and national reference laboratories. These activities require sharing and joint evaluation of surveillance information from laboratory diagnosis, serotyping, genetic characterisation and vaccine matching tests and harmonisation of standards for diagnostic procedures. |
| Impact | Outputs from the network provide vital information to international organisations involved in the control of FMD (such as OIE and FAO), as well as specific regional and national programmes to control FMD |
| Start Year | 2006 |
| Description | Studentship Supervision |
| Organisation | University of Glasgow |
| Department | Institute of Biodiversity, Animal Health and Comparative Medicine |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Co-supervision of PhD student |
| Collaborator Contribution | Co-supervision of PhD student |
| Impact | Multi-disciplinary collaboration to realize the outputs from NGS sequencing analyses of FMDV isolates |
| Start Year | 2012 |
| Description | Diamond (TT) |
| 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 | Diamond Light Source Open Day - explaining to general public the importance of structural biology and microscopy for understanding viruses and designing improved vaccines. |
| Year(s) Of Engagement Activity | 2019 |
| Description | EUROPIC 2014 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Presentation at EUROPIC meeting: Logan G., King D. P., Haydon D. T. and Cottam E. M. Dissection of genetic diversity within virus populations: comparisons between the seven FMDV serotypes using a novel PCR-free NGS approach. 18th International Picornavirus meeting (EUROPIC), Blankenberge, Belgium, March 2014. |
| Year(s) Of Engagement Activity | 2014 |
| Description | EUROPIC 2016 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Presentation provided at EUROPIC: Logan G., Newman J., Wright C. F., Lasecka L., King D. P., Haydon D. T., Cottam E. M. and Tuthill T. J. Virus quasispecies reveals RNA structures required for genome packaging. 19th International Picornavirus Meeting, Les Diablerets, Switzerland, September 2016. |
| Year(s) Of Engagement Activity | 2016 |
| Description | EUROPIC 2016 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Presentation at EUROPIC: Lasecka-Dykes L., Tulloch F., Gold S., Luke G., Wright C. F., Knowles N. J., Logan G., Tuthill T. J., Jackson T. Simmonds P., Ryan M. and King D. P. Prediction of conserved RNA structures the within foot-and-mouth disease virus genome reveals functional cis-acting elements localised in the 3D coding region. 19th International Picornavirus Meeting, Les Diablerets, Switzerland, September 2016. |
| Year(s) Of Engagement Activity | 2016 |
| Description | Invited Keynote Presentation - EPIZONE meeting, Copenhagen |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | A keynote talk was presented to outline the use of new sequencing technologies to understand the epidemiology of FMDV Title of talk: Keynote: King D. P., Logan G., Valdazo-González B., Freimanis G. L., Wright C. F., King D. J., Knowles N. J., Wadsworth J., Bachanek-Bankowska K., Di Nardo A., Orton R., Haydon D. T. The consensus and beyond: developing new tools to reconstruct transmission pathways of foot-and-mouth disease virus. 8th Annual Meeting of the EPIZONE project, Copenhagen, September 2014. |
| Year(s) Of Engagement Activity | 2014 |
| URL | http://www.epizone-eu.net/en/Home/show/8th-Annual-Meeting-Denmark-2014.htm |
| Description | Keynote presentation - 7th International Symposium on Emerging and re-emerging Pig Diseases, Kyoto, Japan |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Presented a talk outlining our research findings - entitled: "King D.P., Logan G., Freimanis G. L., Wright C. F., King D. J., Knowles N. J., Wadsworth J., Lasecka L., Bachanek-Bankowska K., Di Nardo A., Orton R. and Haydon D. T. Using sequence data to understand the epidemiology of foot-and-mouth disease" at the 7th International Symposium on Emerging and re-emerging Pig Diseases, Kyoto, Japan, June 2015. |
| Year(s) Of Engagement Activity | 2015 |
| URL | http://emerging2015.com |
| Description | Korean Vet Soc |
| 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: King D. P., Logan G., Valdazo-González B., Freimanis G. L., Wright C. F., King D. J., Knowles N. J., Wadsworth J., Bachanek-Bankowska K., Di Nardo A., Orton R., Haydon D. T. The consensus and beyond: developing sequencing approaches for FMDV and other RNA viruses. Annual Meeting of the Korean Society of Veterinary Science, Jeju Island, Republic of Korea, October 2014. |
| Year(s) Of Engagement Activity | 2014 |
| Description | SGM 2015 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Postgraduate students |
| Results and Impact | Presentation at SGM: Logan G., Kelly J. D., Lasecka L., Cottam E. M., King D. P., Tuthill T. J. and Haydon D. T. Adaptive evolution of foot-and-mouth disease virus: sub-consensus level genetic diversity influences viral phenotype. Society for General Microbiology Meeting, Birmingham, UK, April 2015. |
| Year(s) Of Engagement Activity | 2015 |