Emerging diseases are a growing global problem, and wildlife pathogens
are the principal source of disease. Human encroachment and climate change are increasing interactions
between wildlife and human communities, leading to greater zoonotic and epizootic spillover. The genetic
similarity of humans and non-human primates (NHPs) provides an opportunity for viruses to impact both
human and animal populations, especially in areas where contact is continuing to increase. Notable
knowledge gaps persist concerning the dynamics and likely routes of viral transmission within such
heterogeneous natural environments. Here, we examine a model pathogen, adenovirus (AdV), common to
humans, NHPs, and many other hosts and sources, to determine and model transmission routes in an
interconnected biodiversity hotspot in East Africa. We will apply next-generation DNA sequencing,
combined with demographic data and advanced phylogenetic analysis techniques, to identify likely
transmission pathways and to model host factors and interactions affecting viral transmission. Our four
main objectives are to: 1) Obtain fine-grained, longitudinal surveillance data on AdV from wild NHPs,
domestic animals, flies, ticks, dung beetles, water, and soil in a natural, heterogeneous spillover hotspot;
2) Apply advanced phylogenetic and bioinformatics tools to next-generation sequencing (NGS) data for
the presence, abundance, variation and routes of transmission of AdV within and among hosts and
environs; 3) Identify source factors impacting viral transmission, e.g., host or source type, proximity,
density, other viruses and pathogens, host evolutionary relationships; 4) Develop prediction models of
how factors (e.g., host species,, phylogeny, proximity, source) influence viral transmission routes, with the
ultimate aim to inform mitigation efforts regarding disease transmission for the benefit of human and
animal health. By focusing on a common, prevalent virus like AdV, we can identify, quantify, model, and
ultimately predict key aspects of viral transmission and the factors affecting spillover in complex natural
environments, which will be applicable for understanding and preventing disease transmission more
broadly. In addition, this research builds capacity and supports broader African and U.S. genomic and
biostatistics training. The knowledge gained will be instrumental for policy decision-making to prevent and
mitigate zoonotic and anthroponotic disease outbreaks and improving quality of life with conservation and
public health benefits.