YY-EEID US-UK The evolutionary ecology of pathogen emergence via cross-species transmission in the avian-equine influenza system
Lead Research Organisation:
University of Glasgow
Department Name: MRC Centre for Virus Research
Abstract
Viral emergence poses a constant threat to humans and animals and we are neither able to predict which viruses will emerge, nor where, when, or which populations will be affected. The overall aim of this project is to determine how environmental, host, and virus factors influence host-pathogen interactions and transmission dynamics of potentially emerging viruses. Avian influenza viruses (AIVs) provide unique opportunities to address this because they have jumped into humans, dogs, pigs and horses, with significant consequences on public health, food security, and the global economy. We will focus on the transmission and emergence of AIVs to horses because AIV strains have emerged in horse populations on independent occasions. We propose to perform field work in a well-defined ecosystem that favours avian-to-horse AIV transmission and also to perform laboratory experiments using avian and equine influenza viruses with different levels of "equine fitness" - ability to infect and transmit in horses. Our laboratory experiments will use genetic engineering to capture changes in fitness due to virus evolution. Results obtained will be combined in a mathematical framework that will enable the estimation of risk of viral emergence, including the effects of herd immunity. This multidisciplinary research will provide new insights on the mechanisms that underpin viral emergence and will aid the design of more effective intervention measures to control future events of viral emergence.
Technical Summary
Generalist pathogens are the norm rather than the exception, with many pathogens, including viruses, capable of infecting host species that are distantly related to each other. For any particular pathogen, our mechanistic understanding of this host range is poor, yet this knowledge can potentially illuminate many host-pathogen association patterns in nature. Moreover, with the majority of emerging infectious diseases caused by zoonoses, identifying the barriers and bridges to cross-species transmission will support public health research and application.
Equine influenza viruses have been postulated as potential pandemic viruses because some virus strains derived from horses can infect humans, at least experimentally. Furthermore, from the 17th to the early 20th century, it has been noted that equine influenza epizootics coincided with major human outbreaks and epidemics. Although the world has replaced the horse as the major mode of transportation and, consequently, decreased the chances of human exposure to horse pathogens, this is not the case in Mongolia. Still to this day, horses play a major role in the lives of Mongols as a major mode of transport and an important source of milk and meat. Mongolia's horse population is ~3 million, similar to its human population size. Thus, Mongolia still is the one place in the world where the emergence of a novel pandemic influenza strain of equine origin is possible. This project will study the fundamental steps leading to novel pathogen emergence in a host species and a well-defined ecosystem through a linked set of research questions to obtain information on 1) dynamics of exposure to pathogens from donor to recipient species, 2) variation in fitness components of emerging and non-emerging pathogens in recipient species, 3) effects of small (mutation) and large (reassortment) genetic changes to pathogen fitness in recipient species, 4) consequences of immunity generated by previous exposures on pathogen emergence.
Equine influenza viruses have been postulated as potential pandemic viruses because some virus strains derived from horses can infect humans, at least experimentally. Furthermore, from the 17th to the early 20th century, it has been noted that equine influenza epizootics coincided with major human outbreaks and epidemics. Although the world has replaced the horse as the major mode of transportation and, consequently, decreased the chances of human exposure to horse pathogens, this is not the case in Mongolia. Still to this day, horses play a major role in the lives of Mongols as a major mode of transport and an important source of milk and meat. Mongolia's horse population is ~3 million, similar to its human population size. Thus, Mongolia still is the one place in the world where the emergence of a novel pandemic influenza strain of equine origin is possible. This project will study the fundamental steps leading to novel pathogen emergence in a host species and a well-defined ecosystem through a linked set of research questions to obtain information on 1) dynamics of exposure to pathogens from donor to recipient species, 2) variation in fitness components of emerging and non-emerging pathogens in recipient species, 3) effects of small (mutation) and large (reassortment) genetic changes to pathogen fitness in recipient species, 4) consequences of immunity generated by previous exposures on pathogen emergence.
Publications
Hofer U
(2022)
Equine flu after the jump.
in Nature reviews. Microbiology
Hosie MJ
(2021)
Detection of SARS-CoV-2 in respiratory samples from cats in the UK associated with human-to-cat transmission.
in The Veterinary record
Wasik BR
(2023)
Understanding the divergent evolution and epidemiology of H3N8 influenza viruses in dogs and horses.
in Virus evolution
Whitlock F
(2022)
A Review on Equine Influenza from a Human Influenza Perspective.
in Viruses
Goldfarb DM
(2022)
Investigations on influenza A virus morphology
Whitlock F
(2022)
A Review on Equine Influenza from a Human Influenza Perspective.
Amat JAR
(2022)
Adaptation of avian-origin influenza virus to the horse
Whitlock F
(2022)
A Review on Equine Influenza from a Human Influenza Perspective.
Description | Discussions on avian influenza preparedness and research gaps |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Description | Invited to a gap analysis meeting on future research priorities of animal influenza |
Geographic Reach | National |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | Participation in Equine Industry Committee (EIC) meeting - 20 September 2022 |
Geographic Reach | National |
Policy Influence Type | Participation in a guidance/advisory committee |
Title | Long-term adaptation following virus host shifts results in higher replication rate, broader intra-host spread and lower pathogenicity |
Description | RNAseq data of equine cells infected with different equine influenza viruses or treated with interferon |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | Not applicable |
URL | https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJEB29313 |
Description | Collaboration with the State Central Laboratory of Mongolia |
Organisation | State Central Veterinary Laboratory |
Country | Mongolia |
Sector | Public |
PI Contribution | We designed the project and provided funding to carry it out. They carry out the field work. |
Collaborator Contribution | The perform field work (surveillance) and send us sera from horses for serological analysis. |
Impact | Not applicable |
Start Year | 2021 |
Description | Established a multidisciplinary research team with University of Georgia and Institute of Biodiversity, Animal Health and Comparative Medicine of the University of Glasgow |
Organisation | University of Georgia |
Country | United States |
Sector | Academic/University |
PI Contribution | We are carrying out a research project and funded NSF/BBSRC. |
Collaborator Contribution | They are an integral part in the design of this new research project. |
Impact | No outputs yet. This collaboration is multidisciplinary as it brings together virologists and mathematical modellers to understand better the basis of host range and the risk of viral emergence. |
Start Year | 2019 |
Description | University of Cambridge-EIV surveillance team |
Organisation | University of Cambridge |
Department | Department of Veterinary Medicine |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Share materials and information about Equine influenza in the United Kingdom. |
Collaborator Contribution | Share materials and information about Equine influenza in the United Kingdom. |
Impact | Not applicable |
Start Year | 2021 |
Description | Equine Industry Committee presentation |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | I presented our Project to the Equine Industry Committee. |
Year(s) Of Engagement Activity | 2022 |
Description | Interview for National News |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | This was a TV interview to cover the first case of swine influenza in a human in the UK. This was covered by ITV. |
Year(s) Of Engagement Activity | 2023 |
Description | Interview for National News- Pablo Murcia on first human case of H1N2 swine flu detected in the UK |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | The intended purpose of this interview was to inform the public of the potential risks posed by H1N2 swine influenza to the general population. |
Year(s) Of Engagement Activity | 2023 |
URL | https://www.itv.com/news/2023-11-27/first-human-case-of-h1n2-swine-flu-detected-in-uk |
Description | PCR workshop for high school students |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | Over 100 High School students from various regions in Scotland attended this PCR workshop organised by the CVR. Students attended a series of short talks and then carried out a laboratory activity that included setting up a PCR, running a gel, interpreting results, BLASTING a sequence, and visualising cells in culture. Students showed interest on the activities and some students raised various questions. |
Year(s) Of Engagement Activity | 2023 |
Description | Presentation about equine influenza epidemiology and spread in the UK to the Equine Industry Committee |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | I gave an update on our project, highlighting the importance of genomic surveillance to control equine influenza. |
Year(s) Of Engagement Activity | 2024 |
Description | School talk |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Schools |
Results and Impact | ~80 high school students attended a talk at a school in Buenos Aires, Argentina. My talk was about careers in research in Biological Sciences. The talk was followed by a Q&A session in which the students were very engaged. |
Year(s) Of Engagement Activity | 2023 |