Beyond discovery: bat behavior and virus shedding as drivers of spillover risk

PROJECT SUMMARY The COVID-19 pandemic has reinforced the significance of emerging infectious diseases for human health and security. Bats have been associated with high-profile viral emergence events, including SARS-CoV-2 (the causative agent of COVID-19), ebolaviruses, and a variety of zoonotic and almost invariably lethal lyssaviruses. While much recent research has investigated virus diversity in bats, it is largely unknown how infection processes in bats and their behavior shape virus exposure risk for other species. Exposure is the obligatory first step for pathogen spillover and one of the strongest points for intervention in the process leading to the emergence of new human diseases. Further, bat displacements are commonly used to mitigate human risks posed by bat- borne viruses in low-income settings. Yet, how displacements and other perturbations affect viral exposure and spillover risk is not known, largely because the necessary longitudinal monitoring is rarely undertaken and is frustrated by challenges of appropriate controls and monitoring rare viruses in difficult to capture animals. This project will focus on three important and unusually tractable host-virus systems: coronaviruses, rabies virus, and Bombali ebolavirus in their wild bat hosts in Taita Hills, Kenya and Orange Walk, Belize. We will use a combination of longitudinal monitoring, bat behavior studies, and field experiments to examine how virus shedding dynamics in bat populations and bat use of anthropogenic structures shape virus exposure risk for humans and domestic animals that can act as intermediate hosts. To explore generalizability across viruses and assess whether perturbation triggers the shedding of latent viruses, we will further use proteomic and metagenomic approaches to characterize stress and immunological responses to perturbations and measure viral diversity shifts at a community level. Our multidisciplinary approach will confront field-collected virus serological, shedding, and sequence data with competing epidemiological models to elucidate fundamental principles driving viral infection and shedding from bats (aim 1); employ anthropogenic roost selection and use surveys to identify local- and landscape-level areas where human encounters with bats and virus are greatest (aim 2); and conduct controlled experimental displacements of wild bats through roost evictions to quantify the responses of bat stress, immunity, and viral communities to this common occurrence (aim 3). Together, these studies will represent an unusually comprehensive and detailed investigation into the dynamics of viruses in wild bat populations and provide a critical advance towards evidence-based risk evaluation and prevention.