Integrating metavBB/Y006879/1iromics with epidemiological dynamics: understanding rodent virus transmission in the Anthropocene

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.