title: Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone.
abstract: The 2013-2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV within the region and describe viral evolution during prolonged human-to-human transmission.
authors.affiliation: Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA. Electronic address: dpark@broadinstitute.org.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Park
authors.affiliation: Institute of Evolutionary Biology, Ashworth Laboratories, University of Edinburgh, Edinburgh EH9 3FL, UK.
authors.forename: Gytis
authors.initials: G
authors.lastname: Dudas
authors.affiliation: Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA; Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
authors.forename: Shirlee
authors.initials: S
authors.lastname: Wohl
authors.affiliation: Kenema Government Hospital, Kenema, Sierra Leone.
authors.forename: Augustine
authors.initials: A
authors.lastname: Goba
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Shannon L M
authors.initials: SL
authors.lastname: Whitmer
authors.affiliation: Scripps Translational Science Institute, The Scripps Research Institute, 3344 N Torrey Pines Court, La Jolla, CA 92037, USA.
authors.forename: Kristian G
authors.initials: KG
authors.lastname: Andersen
authors.affiliation: Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA; Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Rachel S
authors.initials: RS
authors.lastname: Sealfon
authors.affiliation: US Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Jason T
authors.initials: JT
authors.lastname: Ladner
authors.affiliation: US Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Kugelman
authors.affiliation: Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA.
authors.forename: Christian B
authors.initials: CB
authors.lastname: Matranga
authors.affiliation: Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA; Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Winnicki
authors.affiliation: Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA.
authors.forename: James
authors.initials: J
authors.lastname: Qu
authors.affiliation: Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA; Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Gire
authors.affiliation: Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA.
authors.forename: Adrianne
authors.initials: A
authors.lastname: Gladden-Young
authors.affiliation: Kenema Government Hospital, Kenema, Sierra Leone.
authors.forename: Simbirie
authors.initials: S
authors.lastname: Jalloh
authors.affiliation: Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA.
authors.forename: Dolo
authors.initials: D
authors.lastname: Nosamiefan
authors.affiliation: Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA; Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
authors.forename: Nathan L
authors.initials: NL
authors.lastname: Yozwiak
authors.affiliation: Tulane University, 1430 Tulane Avenue, SL-38, New Orleans, LA 70112, USA.
authors.forename: Lina M
authors.initials: LM
authors.lastname: Moses
authors.affiliation: Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA; Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
authors.forename: Pan-Pan
authors.initials: PP
authors.lastname: Jiang
authors.affiliation: Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA; Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
authors.forename: Aaron E
authors.initials: AE
authors.lastname: Lin
authors.affiliation: Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA; Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Schaffner
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Bird
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Towner
authors.affiliation: Kenema Government Hospital, Kenema, Sierra Leone.
authors.forename: Mambu
authors.initials: M
authors.lastname: Mamoh
authors.affiliation: Kenema Government Hospital, Kenema, Sierra Leone.
authors.forename: Michael
authors.initials: M
authors.lastname: Gbakie
authors.affiliation: Kenema Government Hospital, Kenema, Sierra Leone.
authors.forename: Lansana
authors.initials: L
authors.lastname: Kanneh
authors.affiliation: Kenema Government Hospital, Kenema, Sierra Leone.
authors.forename: David
authors.initials: D
authors.lastname: Kargbo
authors.affiliation: Kenema Government Hospital, Kenema, Sierra Leone.
authors.forename: James L B
authors.initials: JL
authors.lastname: Massally
authors.affiliation: Kenema Government Hospital, Kenema, Sierra Leone.
authors.forename: Fatima K
authors.initials: FK
authors.lastname: Kamara
authors.affiliation: Kenema Government Hospital, Kenema, Sierra Leone.
authors.forename: Edwin
authors.initials: E
authors.lastname: Konuwa
authors.affiliation: Kenema Government Hospital, Kenema, Sierra Leone.
authors.forename: Josephine
authors.initials: J
authors.lastname: Sellu
authors.affiliation: Kenema Government Hospital, Kenema, Sierra Leone.
authors.forename: Abdul A
authors.initials: AA
authors.lastname: Jalloh
authors.affiliation: Kenema Government Hospital, Kenema, Sierra Leone.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Mustapha
authors.affiliation: Kenema Government Hospital, Kenema, Sierra Leone.
authors.forename: Momoh
authors.initials: M
authors.lastname: Foday
authors.affiliation: Kenema Government Hospital, Kenema, Sierra Leone.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Yillah
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Bobbie R
authors.initials: BR
authors.lastname: Erickson
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Tara
authors.initials: T
authors.lastname: Sealy
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Dianna
authors.initials: D
authors.lastname: Blau
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Paddock
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Brault
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Amman
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Basile
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Bearden
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Belser
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Bergeron
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Shelley
authors.initials: S
authors.lastname: Campbell
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Ayan
authors.initials: A
authors.lastname: Chakrabarti
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Dodd
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Mike
authors.initials: M
authors.lastname: Flint
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
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authors.initials: A
authors.lastname: Gibbons
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Christin
authors.initials: C
authors.lastname: Goodman
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: John
authors.initials: J
authors.lastname: Klena
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: McMullan
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Morgan
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Brandy
authors.initials: B
authors.lastname: Russell
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Johanna
authors.initials: J
authors.lastname: Salzer
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Sanchez
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: David
authors.initials: D
authors.lastname: Wang
authors.affiliation: Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Irwin
authors.initials: I
authors.lastname: Jungreis
authors.affiliation: Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Tomkins-Tinch
authors.affiliation: DNAnexus, 1975 West El Camino Real, Suite 101, Mountain View, CA 94040, USA.
authors.forename: Andrey
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authors.affiliation: DNAnexus, 1975 West El Camino Real, Suite 101, Mountain View, CA 94040, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Lin
authors.affiliation: Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA.
authors.forename: Sinead
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authors.lastname: Chapman
authors.affiliation: Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA.
authors.forename: Bronwyn
authors.initials: B
authors.lastname: MacInnis
authors.affiliation: Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA; Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
authors.forename: Ashley
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authors.lastname: Matthews
authors.affiliation: Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA.
authors.forename: James
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authors.lastname: Bochicchio
authors.affiliation: Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, B-8200 Research Plaza, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Hensley
authors.affiliation: Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, B-8200 Research Plaza, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Jens H
authors.initials: JH
authors.lastname: Kuhn
authors.affiliation: Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA.
authors.forename: Chad
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authors.lastname: Nusbaum
authors.affiliation: Tulane University, 1430 Tulane Avenue, SL-38, New Orleans, LA 70112, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Schieffelin
authors.affiliation: Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA.
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Birren
authors.affiliation: Médecins Sans Frontières, Rue de l'Arbre Bénit 46, 1050 Bruxelles, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Forget
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Stuart T
authors.initials: ST
authors.lastname: Nichol
authors.affiliation: US Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Gustavo F
authors.initials: GF
authors.lastname: Palacios
authors.affiliation: Université Cheikh Anta Diop, BP 5005, Dakar, Sénégal.
authors.forename: Daouda
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authors.lastname: Ndiaye
authors.affiliation: Redeemers University Nigeria, KM 46 Lagos-Ibadan Expressway, Redemption City, Ogun State, Nigeria.
authors.forename: Christian
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authors.lastname: Happi
authors.affiliation: University of Sierra Leone, A.J. Momoh St, Tower Hill, Freetown, Sierra Leone.
authors.forename: Sahr M
authors.initials: SM
authors.lastname: Gevao
authors.affiliation: Sierra Leone Ministry of Health and Sanitation, Youyi Building, Freetown, Sierra Leone.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Vandi
authors.affiliation: Sierra Leone Ministry of Health and Sanitation, Youyi Building, Freetown, Sierra Leone.
authors.forename: Brima
authors.initials: B
authors.lastname: Kargbo
authors.affiliation: University of Sydney, Johns Hopkins Drive, Camperdown NSW 2050, Australia.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Holmes
authors.affiliation: Fred Hutchinson Cancer Research Center, 110 Fairview Avenue North, Seattle, WA 98109, USA.
authors.forename: Trevor
authors.initials: T
authors.lastname: Bedford
authors.affiliation: Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Gnirke
authors.affiliation: National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA.
authors.forename: Ute
authors.initials: U
authors.lastname: Ströher
authors.affiliation: Institute of Evolutionary Biology, Ashworth Laboratories, University of Edinburgh, Edinburgh EH9 3FL, UK; Centre for Immunology, Infection and Evolution, University of Edinburgh, Ashworth Laboratories, Edinburgh EH9 3FL, UK; Fogarty International Center, National Institutes of Health, 31 Center Drive, MSC 2220 Bethesda, MD 20892, USA. Electronic address: a.rambaut@ed.ac.uk.
authors.forename: Andrew
authors.initials: A
authors.lastname: Rambaut
authors.affiliation: Tulane University, 1430 Tulane Avenue, SL-38, New Orleans, LA 70112, USA.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Garry
authors.affiliation: Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA; Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA. Electronic address: pardis@broadinstitute.org.
authors.forename: Pardis C
authors.initials: PC
authors.lastname: Sabeti
mesh_terms: D005075:Biological Evolution; D004196:Disease Outbreaks; D029043:Ebolavirus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification*; D016679:Genome, Viral; D019142:Hemorrhagic Fever, Ebola / Q000453:epidemiology* / Q000635:transmission / Q000821:virology*; D006801:Humans; D009154:Mutation; D012807:Sierra Leone / Q000453:epidemiology; D013048:Specimen Handling