@article{0acd9330b7374c0599b127f04b6b7635,
title = "Active Ebola Virus Replication and Heterogeneous Evolutionary Rates in EVD Survivors",
abstract = "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 = "EVD survivors, Ebola virus, RNA hyper-editing, evolutionary pressure, evolutionary rates, persistent viral infection",
author = "{Ebola Virus Persistence Study Group} and Whitmer, {Shannon L.M.} and Ladner, {Jason T.} and Wiley, {Michael R.} and Ketan Patel and Gytis Dudas and Andrew Rambaut and Foday Sahr and Karla Prieto and Shepard, {Samuel S.} and Ellie Carmody and Barbara Knust and Dhamari Naidoo and Gibrilla Deen and Pierre Formenty and Nichol, {Stuart T.} and Gustavo Palacios and Ute Str{\"o}her",
note = "Funding Information: The authors acknowledge William Davis (CDC/NCEZID/VSPB), Amy Schuh (CDC/NCEZID/VSPB), Serena Carroll (CDC/NCEZID), and Mark Whitmer (The NerdWerks, LLC) for their thoughtful review and discussion. The authors acknowledge Mike Purdy (CDC/NCHHSTP), William Fischer (LANL), and Mark Whitmer (The NerdWerks, LLC) for their software and script assistance. Work at US Army Medical Research Institute of Infectious Diseases was funded by the Defense Threat Reduction Agency , project CB10246 . Financial support provided by the WHO , the CDC , the China CDC , the Paul G. Allen Family Foundation , the Sierra Leone Ministry of Health and Sanitation , and the Joint United Nations Program on HIV/AIDS . The WHO acknowledges the financial contribution of the WHO Ebola Response Program , the Paul G. Allen Family Foundation , the UNDP (United Nations Development Program), UNFPA (United Nations Population Fund), UNICEF WHO , World Bank Special Program of Research, Development and Research Training in Human Reproduction (HRP), a cosponsored program executed by the WHO in support of the Sierra Leone Ebola Virus Persistence Study. The authors acknowledge the Emory University Serious Communicable Diseases Program; the Military Hospital 34 and Lungi General Hospital staff; the Sierra Leone Association of Ebola Survivors: Yusuf Kabba; WHO: Ian Askew, Bruce Aylward, Rachel Baggaley, Anshu Banerjee, George Bindi, Rick Brennan, Mauricio Calderon, Ian Crozier, Christopher Dye, Peter Graaff, James N. Kiarie, Marie-Paule Kieny, Anders Nordstr{\"o}m, Collins Owili, Lee Sharkey, and Lisa Thomas; and the US-CDC: Dianna Blau (IDP), Aaron Brault (ADB), Jorn Winter (VSDB), Tara Sealy (VSPB), John D. Klena (VSPB), and Lance Presser (VSPB). The content of this publication does not necessarily reflect the views or policies of the US Army. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of CDC. Funding Information: The authors acknowledge William Davis (CDC/NCEZID/VSPB), Amy Schuh (CDC/NCEZID/VSPB), Serena Carroll (CDC/NCEZID), and Mark Whitmer (The NerdWerks, LLC) for their thoughtful review and discussion. The authors acknowledge Mike Purdy (CDC/NCHHSTP), William Fischer (LANL), and Mark Whitmer (The NerdWerks, LLC) for their software and script assistance. Work at US Army Medical Research Institute of Infectious Diseases was funded by the Defense Threat Reduction Agency, project CB10246. Financial support provided by the WHO, the CDC, the China CDC, the Paul G. Allen Family Foundation, the Sierra Leone Ministry of Health and Sanitation, and the Joint United Nations Program on HIV/AIDS. The WHO acknowledges the financial contribution of the WHO Ebola Response Program, the Paul G. Allen Family Foundation, the UNDP (United Nations Development Program), UNFPA (United Nations Population Fund), UNICEF WHO, World Bank Special Program of Research, Development and Research Training in Human Reproduction (HRP), a cosponsored program executed by the WHO in support of the Sierra Leone Ebola Virus Persistence Study. The authors acknowledge the Emory University Serious Communicable Diseases Program; the Military Hospital 34 and Lungi General Hospital staff; the Sierra Leone Association of Ebola Survivors: Yusuf Kabba; WHO: Ian Askew, Bruce Aylward, Rachel Baggaley, Anshu Banerjee, George Bindi, Rick Brennan, Mauricio Calderon, Ian Crozier, Christopher Dye, Peter Graaff, James N. Kiarie, Marie-Paule Kieny, Anders Nordstr{\"o}m, Collins Owili, Lee Sharkey, and Lisa Thomas; and the US-CDC: Dianna Blau (IDP), Aaron Brault (ADB), Jorn Winter (VSDB), Tara Sealy (VSPB), John D. Klena (VSPB), and Lance Presser (VSPB). The content of this publication does not necessarily reflect the views or policies of the US Army. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of CDC. Publisher Copyright: {\textcopyright} 2018",
year = "2018",
month = jan,
day = "30",
doi = "10.1016/j.celrep.2018.01.008",
language = "English (US)",
volume = "22",
pages = "1159--1168",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "5",
}