22-EEID US-UK Collab: Integrating metaviromics with epidemiological dynamics: understanding rodent virus transmission in the Anthropocene

Lead Research Organisation: Royal Veterinary College
Department Name: Pathobiology and Population Sciences

Abstract

Most emerging infectious diseases affecting humans, including AIDS, influenza, and COVID-19, are caused by RNA viruses originating from non-human animals. In recent years, such 'zoonotic' viral diseases have become more common and widespread, a pattern frequently attributed to increasing environmental change. Notably, escalating human activity has destroyed and disrupted wild animal habitats by converting natural landscapes into agricultural farmlands and urban environments. As a result, we have drastically altered wild animal communities and how viruses circulate within these communities while simultaneously increasing our exposure to new animal viruses by eliminating historical ecological barriers separating species. Temporal changes in the environment, such as seasonal variation or climate change, can also alter pathogen prevalence in wild animal populations and influence zoonotic risk.

Despite significant research on viral zoonoses, actionable, real-world predictions of virus spillover risk remain elusive. A critical barrier to preventing and controlling future viral zoonoses is a lack of basic knowledge about how physical and temporal differences in the environment impact virus transmission within wild animal populations and how changes in viral transmission and community composition translate to human risk.

Attaining a predictive understanding of the dynamics of zoonoses within their animal reservoirs is a precondition to anticipate emergence or devise interventions that prevent emergence. However, financial and logistical challenges in studying high-risk viruses in wild animals - from the need for regular monitoring of individuals to the costly biosafety precautions involved - currently impede such understanding in most wildlife disease systems.

We will address these challenges by focusing on wild rodents, which are important viral reservoirs globally, responsible for more zoonoses than any other mammalian order, and represent well-studied and tractable systems for understanding the environmental impact on zoonotic virus transmission. Many rodents live in close proximity to human populations and are highly responsive to environmental change, both in their population dynamics and via behavioural changes that increase contact with humans. However, despite this circumstantial evidence, the underlying ecological mechanisms driving virus transmission within wild rodent populations remain hypothetical and, importantly, are far from predictive. This project will investigate how viruses circulate in wild rodents using established field studies in England and Uganda, which monitor wild rodent communities over time and space:

1) To tackle the practical challenges of studying viral transmission, we will develop new tools to infer epidemiological dynamics and zoonotic risk from increasingly accessible and low-cost host virome data. This flexible approach will allow rapid discovery and monitoring of zoonotic viruses by enabling epidemiological inferences from cross-sectional samples and guidance for appropriate sampling strategies to interpret metaviromic data in new host systems.

2) Using a long-term capture-mark-recapture wild study in Oxfordshire, UK, we will determine how seasonal environmental change influences rodent viral communities.

3) We will use field sites along a gradient of land cover in Uganda to understand how physical environmental change influences the risk of zoonotics in rodent communities. Specifically, we will identify local and landscape drivers of zoonotic hazards and how humans change behaviour to affect zoonotic risk across this gradient.

Together, this research will substantially improve our understanding of viral pathogens within key reservoir hosts and identify important environmental drivers that increase zoonotic risk.

Technical Summary

Decreasing costs and increasing efficiency of metagenomic sequencing have rapidly expanded our knowledge of global virus diversity, particularly in well-known zoonotic reservoir species, such as rodents and bats. However, despite these advances, we cannot leverage this knowledge to shed light on virus transmission within reservoir populations -consequently, our ability to evaluate where, whence, and which viruses present the highest zoonotic risk. There are two outstanding challenges to this knowledge gap. First, longitudinal and spatially representative sampling in viral metagenomic studies is extremely rare, with most studies representing a single snapshot in time and space, limiting their use in studying transmission dynamics. Second, we lack a framework linking the composition of the virus community and the underlying transmission dynamics in the reservoir to the zoonotic risk.

We will address these obstacles by capitalising on established, tractable wild rodent field studies across changing environments and advancing epidemiological theory by integrating metaviromic data with mechanistic models of virus transmission. Specifically, we will (i) develop, implement and validate a methodological framework to infer epidemiological dynamics and zoonotic hazards from cross-sectional metaviromic data, (ii) identify environmental and ecological drivers of rodent virus transmission and zoonotic hazards in seasonally varying habitats using real-time microclimate, social network, and population data, and (iii) Using an existing gradient of land cover, quantify how anthropogenic land-use change shapes host demography, virus diversity, and transmission dynamics.

With this multidisciplinary approach, this research will provide new insights into the dynamics of virus transmission in wild animals across space and time and help advance our understanding of zoonotic risk in a rapidly changing world.

Publications

10 25 50
 
Description Developing and deploying methods to measure rodent movement to inform zoonotic hazard
Amount £87,713 (GBP)
Funding ID BB/Y514251/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 03/2024 
End 06/2024
 
Description Glasgow Early Career Mobility Scheme 2024-2025
Amount £4,932 (GBP)
Organisation University of Glasgow 
Sector Academic/University
Country United Kingdom
Start 11/2024 
End 07/2025
 
Description Collaborative One Health Research Initiative on Epidemics (COHRIE) 
Organisation Uganda National Health Research Organisation
Country Uganda 
Sector Public 
PI Contribution We hosted COHRIE members in the field and trained them in capture-mark recapture in January 2025
Collaborator Contribution COHRIE members met with Glasgow and Vector Control Division in August 2024 in Entebbe for knowledge exchange.
Impact Currently seeking funding to support more field activities and personnel
Start Year 2024
 
Description Rodent Metaviromics Consoritium 
Organisation Duke-NUS Graduate Medical School
Department Microbiology Duke-NUS
Country United States 
Sector Academic/University 
PI Contribution We set up the network in September 2024 between multiple groups using similar genomic approaches to characterise small mammal viromes and understand environmental and ecological drivers of rodent virus spillover. The aim of this network is to foster knowledge exchange between research groups working in complementary areas, for example to discussing and getting feedback on preliminary findings. Our research team presented their research on understanding relationship between metaviromic and viral load data.
Collaborator Contribution The other partners provided feedback on the first meeting, and Sophie Gryseels (University of Antwerp) will present her team's work on using metaviromics for virus surveillance and understanding virus ecology.
Impact Knowledge exchange and intellectual input on research related to metaviromics and rodent virus ecology
Start Year 2024
 
Description Rodent Metaviromics Consoritium 
Organisation Natural History Museum
Department Parasites and Vectors
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution We set up the network in September 2024 between multiple groups using similar genomic approaches to characterise small mammal viromes and understand environmental and ecological drivers of rodent virus spillover. The aim of this network is to foster knowledge exchange between research groups working in complementary areas, for example to discussing and getting feedback on preliminary findings. Our research team presented their research on understanding relationship between metaviromic and viral load data.
Collaborator Contribution The other partners provided feedback on the first meeting, and Sophie Gryseels (University of Antwerp) will present her team's work on using metaviromics for virus surveillance and understanding virus ecology.
Impact Knowledge exchange and intellectual input on research related to metaviromics and rodent virus ecology
Start Year 2024
 
Description Rodent Metaviromics Consoritium 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution We set up the network in September 2024 between multiple groups using similar genomic approaches to characterise small mammal viromes and understand environmental and ecological drivers of rodent virus spillover. The aim of this network is to foster knowledge exchange between research groups working in complementary areas, for example to discussing and getting feedback on preliminary findings. Our research team presented their research on understanding relationship between metaviromic and viral load data.
Collaborator Contribution The other partners provided feedback on the first meeting, and Sophie Gryseels (University of Antwerp) will present her team's work on using metaviromics for virus surveillance and understanding virus ecology.
Impact Knowledge exchange and intellectual input on research related to metaviromics and rodent virus ecology
Start Year 2024
 
Description Rodent Metaviromics Consoritium 
Organisation University of Antwerp
Country Belgium 
Sector Academic/University 
PI Contribution We set up the network in September 2024 between multiple groups using similar genomic approaches to characterise small mammal viromes and understand environmental and ecological drivers of rodent virus spillover. The aim of this network is to foster knowledge exchange between research groups working in complementary areas, for example to discussing and getting feedback on preliminary findings. Our research team presented their research on understanding relationship between metaviromic and viral load data.
Collaborator Contribution The other partners provided feedback on the first meeting, and Sophie Gryseels (University of Antwerp) will present her team's work on using metaviromics for virus surveillance and understanding virus ecology.
Impact Knowledge exchange and intellectual input on research related to metaviromics and rodent virus ecology
Start Year 2024
 
Description University of Antwerp 
Organisation University of Antwerp
Country Belgium 
Sector Academic/University 
PI Contribution We extracted, preparred libraries and sequenced DNA from Mastomys samples from Uganda and Tanzania
Collaborator Contribution Provided samples and datasets for Tanzanian Mastomys
Impact Currently analyzing sequence data
Start Year 2024
 
Description Talk (Abingdon) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Gave a talk on the Wytham rodent project to the Abingdon Naturalists Society
Year(s) Of Engagement Activity 2024