Active Ebola Virus Replication and Heterogeneous Evolutionary Rates in EVD Survivors

Abstract

Summary: Following cessation of continuous Ebola virus (EBOV) transmission within Western Africa, sporadic EBOV disease (EVD) cases continued to re-emerge beyond the viral incubation period. Epidemiological and genomic evidence strongly suggests that this represented transmission from EVD survivors. To investigate whether persistent infections are characterized by ongoing viral replication, we sequenced EBOV from the semen of nine EVD survivors and a subset of corresponding acute specimens. EBOV evolutionary rates during persistence were either similar to or reduced relative to acute infection rates. Active EBOV replication/transcription continued during convalescence, but decreased over time, consistent with viral persistence rather than viral latency. Patterns of genetic divergence suggest a moderate relaxation of selective constraints within the sGP carboxy-terminal tail during persistent infections, but do not support widespread diversifying selection. Altogether, our data illustrate that EBOV persistence in semen, urine, and aqueous humor is not a quiescent or latent infection. : Whitmer et al. find that Ebola virus continues replication/transcription within the eye and male genital tract of Ebola virus disease survivors. They describe viral replication, evolutionary rates, and selective pressures experienced during acute and persistent infection. Keywords: Ebola virus, EVD survivors, persistent viral infection, evolutionary pressure, evolutionary rates, RNA hyper-editing