Assessing mechanisms for the persistence of RNA viruses in bats using a captive and wild Eidolon helium colonies - PROJECT SUMMARY/ABSTRACT Emerging viruses are an important threat to humans, with serious implications for both public health and the global economy. These viruses have emerged from having stable relationships with other animals, and although the spillovers can occur anywhere, studies have shown that there are geographic hotspots (e.g., high diversity ecosystems with frequent interactions between animals and humans) where emergence is more common, and all of these hotpots are located outside of the United States (US). However, because of the interconnectedness of the global economy, emerging viruses can rapidly spread and directly impact the US by causing an outbreak that could originate from anywhere in the world (e.g., the COVID-19 pandemic). Bats, in particular, have been linked to many high consequence emerging viruses, including SARS coronaviruses, as well as filoviruses, Hendra and Nipah viruses. This proposal seeks to address fundamental knowledge gaps regarding bat-hosted viruses through an innovative combination of longitudinal molecular surveillance, highlymultiplexed serology, and whole genome virus sequencing. The study will utilize straw-colored fruit bat (Eidolon helvum) as a model system for studying mechanisms of virus persistence and transmission within bats. E. helvum is widely distributed throughout the West and Central African hotspots for virus emergence, known to host a variety of viruses from groups with known capacity for human infection, and there are multiple documented interfaces for the transmission of viruses from E. helvum to humans, livestock, and other wild animals. Specifically, we propose to work in Accra, Ghana because of the long-term captive breeding colony of E. helvum that has been maintained at the Accra Zoo for research purposes. This globally unique facility will enable us to longitudinally track individual bats and their viruses, in a manner that is not possible when working only with wild populations. Since the facility is located within E. helvum’s endemic range, the impact of population size on virus diversity and shedding can also be directly tested by comparing the captive colony with geographically proximal wild bat populations, something that would not be possible to replicate within the US. Longitudinal sample collection and broad-range PCR will be used to monitor virus shedding over time, and highly-multiplexed serology will be used to obtain an unprecedented view of the viruses infecting E. helvum bats. Differences in infection histories between captive and wild animals will be identified, and whole genome sequencing will be used to track the evolution of viruses shed in the captive colony (with individual-level resolution) and those circulating in wild bats. By providing fundamental knowledge about the dynamics of zoonotic viruses within their natural hosts, this project will help in the design of targeted diagnostics, vaccines, and spillover risk mitigation strategies against viral diseases in the US including rabies, Camp Hill virus (a recently identified henipavirus in Alabama), and other henipaviruses infections, and protect the US population from the damaging impacts of these viruses.