Evidence of latency reshapes our understanding of Ebola virus reservoir dynamics

Abstract

Ebola virus (EBOV) has caused severe outbreaks of haemorrhagic fever in Central and West Africa since the first observed zoonotic epidemic in the late 1970s. While recent outbreaks have revealed much about the epidemiological dynamics that sustain human-to-human transmission, the mechanisms by which the virus persists between outbreaks are unknown. Previously, phylogenetic approaches have been used to characterise the EBOV reservoir from the evolutionary relationships among observed human outbreaks. We here employ a novel phylogenetic latency model - inspired by recent observations of extreme EBOV evolutionary rate heterogeneity in humans - to characterise the natural history of EBOV and by extension its reservoir. We find the prevailing model of EBOV reservoir dynamics is deficient, and the long-term EBOV evolutionary rate is slower than previously believed. The hypothesis that EBOV diversity dates back to a bottleneck event just prior to the first human outbreak is not supported by the data. Further, our results suggest that EBOV undergoes extended periods of quiescence in the reservoir, similar to that observed in a small fraction of human infections. These findings have significant implications for understanding the source of EBOV outbreaks, characterising the EBOV reservoir, and uncovering the factors that contribute to EBOV outbreaks in humans.