Where is the elusive primary ebolavirus reservoir and how do we find It?

An enduring mystery in Ebolavirus research is what host species maintain the virus in the wild. Despite the efforts of multiple research groups over decades, no primary reservoir has ever been identified. To the contrary, finding any evidence of infections in wild mammal populations is exceedingly rare. This is puzzling, given the wide range of species that ebolaviruses infect in laboratory and natural settings. We describe epidemiological, ecological, and immunological factors that have likely stymied the efforts of previous workers. We synthesize observations about host life history and seasonal variation in a key resource to provide recommendations for the geographic locations, species, and sampling regimes likely to prove most profitable for future sampling efforts. Our work also illustrates how a One Health perspective, which considers the dynamics of both wild animal hosts and the environments in which they are embedded, can lend clarity to otherwise seemingly intractable epidemiological problems.