Active Ebola Virus Replication and Heterogeneous Evolutionary Rates in EVD Survivors
Shannon L.M. Whitmer,
Jason T. Ladner,
Michael R. Wiley,
Ketan Patel,
Gytis Dudas,
Andrew Rambaut,
Foday Sahr,
Karla Prieto,
Samuel S. Shepard,
Ellie Carmody,
Barbara Knust,
Dhamari Naidoo,
Gibrilla Deen,
Pierre Formenty,
Stuart T. Nichol,
Gustavo Palacios,
Ute Ströher
Affiliations
Shannon L.M. Whitmer
Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA; Corresponding author
Jason T. Ladner
Center for Genome Sciences, US Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA
Michael R. Wiley
Center for Genome Sciences, US Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA
Ketan Patel
Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA
Gytis Dudas
Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Andrew Rambaut
Institute of Evolutionary Biology, University of Edinburgh, King’s Buildings, Edinburgh, UK; Fogarty International Center, National Institutes of Health, Bethesda, MD, USA
Foday Sahr
Sierra Leone Armed Forces, Freetown, Sierra Leone
Karla Prieto
Center for Genome Sciences, US Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA
Samuel S. Shepard
Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA
Ellie Carmody
Division of Infectious Diseases, NYU School of Medicine, Bellevue Hospital Center, New York, NY, USA
Barbara Knust
Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA
Dhamari Naidoo
Health Emergency Programme, World Health Organization, Geneva, Switzerland
Gibrilla Deen
Sierra Leone Ministry of Health and Sanitation, Freetown, Sierra Leone
Pierre Formenty
Health Emergency Programme, World Health Organization, Geneva, Switzerland
Stuart T. Nichol
Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA
Gustavo Palacios
Center for Genome Sciences, US Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA
Ute Ströher
Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA; Corresponding author
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
