Pathogen Transmission Dynamics among Wildlife and Human Settlements in Rural Western Uganda - Emerging diseases are a growing global problem, and wildlife pathogens are the principal source of disease. Interactions between wildlife and human communities are on the increase, 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. Specific Aims Section Our central hypothesis is that variation in AdV strains and distribution provides an effective means of identifying, tracking, predicting, and ultimately limiting pathways for disease transmission. These invaluable insights, integrative analyses and predictive potential can be extrapolated to model transmission of other, less common, but potentially more dangerous viruses to mitigate disease transmission. Specifically, we hypothesize that: 1) Phylogenetic analyses of viral variation can be used to identify host origins and routes of transmission, generally and under changing natural and anthropogenic conditions; 2) The prevalence of anthroponotic or zoonotic virus transmission is greater among organisms that share proximity (e.g., cattle or chickens); and 3) Viral transmission is predicted to be more prevalent among organisms that share closer evolutionary relationships (e.g., Catarrhine monkeys). To address these hypotheses, we have three main objectives: 1) Use molecular approaches to detect and identify the presence and abundance of AdVs among interconnected wild and domestic animal and insect hosts and the environment in rural Western Uganda; 2) Apply bioinformatic and computational analyses of AdV genomes to identify the presence, identity, abundance, and variation of AdV strains, and then applying phylogenetic and phylodynamic analyses of AdVs to identify routes of viral transmission within and between host species and environs;
