Ebola virus persistence: implications for human-to-human transmission and new outbreaks

Ebola virus (EBOV) infection usually leads to highly lethal EBOV disease (EVD) with associated viraemia. Viraemia is cleared in those that do survive, however, EBOV may remain hidden in the testes and other immune privileged niches (IPNs) where it can persist for years during asymptomatic convalescence. Viral shedding into seminal fluid may result in sexual transmission to naive contacts years after EBOV outbreaks have been declared over. This leads to flare-ups of cases, redefining our understanding of the shaping and origin of EBOV outbreaks. Such delayed sexual transmission eliminates the geographical boundaries which typically constrain EBOV outbreaks, thus posing a significant global health security threat. Despite hints of EBOV persistence dating over half a century, it was only until the unprecedented scale of the 2013–2016 Western Africa EBOV epidemic that the true importance of this phenomenon was revealed to scientists, public health officials and policy makers alike. This review summarises the evidence for EBOV persistence, suggests the possible underlying molecular mechanisms and proposes future directions for research in the field. A meta-analysis is presented to further investigate the duration of EBOV shedding in seminal fluid. The ultimate aim is to develop therapeutics that clear sites of persistence. Such therapeutics could prevent the re-emergence of the persistent virus, eliminating the chance of new outbreaks whilst alleviating the severe stigmatisation facing the EBOV survivor population.