Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone
Identifieur interne : 000141 ( Pmc/Checkpoint ); précédent : 000140; suivant : 000142Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone
Auteurs : Daniel J. Park [États-Unis] ; Gytis Dudas [Royaume-Uni] ; Shirlee Wohl [États-Unis] ; Augustine Goba [Sierra Leone] ; Shannon L. M. Whitmer [États-Unis] ; Kristian G. Andersen [États-Unis] ; Rachel S. Sealfon [États-Unis] ; Jason T. Ladner [États-Unis] ; Jeffrey R. Kugelman [États-Unis] ; Christian B. Matranga [États-Unis] ; Sarah M. Winnicki [États-Unis] ; James Qu [États-Unis] ; Stephen K. Gire [États-Unis] ; Adrianne Gladden-Young [États-Unis] ; Simbirie Jalloh [Sierra Leone] ; Dolo Nosamiefan [États-Unis] ; Nathan L. Yozwiak [États-Unis] ; Lina M. Moses [États-Unis] ; Pan-Pan Jiang [États-Unis] ; Aaron E. Lin [États-Unis] ; Stephen F. Schaffner [États-Unis] ; Brian Bird [États-Unis] ; Jonathan Towner [États-Unis] ; Mambu Mamoh [Sierra Leone] ; Michael Gbakie [Sierra Leone] ; Lansana Kanneh [Sierra Leone] ; David Kargbo [Sierra Leone] ; James L. B. Massally [Sierra Leone] ; Fatima K. Kamara [Sierra Leone] ; Edwin Konuwa [Sierra Leone] ; Josephine Sellu [Sierra Leone] ; Abdul A. Jalloh [Sierra Leone] ; Ibrahim Mustapha [Sierra Leone] ; Momoh Foday [Sierra Leone] ; Mohamed Yillah [Sierra Leone] ; Bobbie R. Erickson [États-Unis] ; Tara Sealy [États-Unis] ; Dianna Blau [États-Unis] ; Christopher Paddock [États-Unis] ; Aaron Brault [États-Unis] ; Brian Amman [États-Unis] ; Jane Basile [États-Unis] ; Scott Bearden [États-Unis] ; Jessica Belser [États-Unis] ; Eric Bergeron [États-Unis] ; Shelley Campbell [États-Unis] ; Ayan Chakrabarti [États-Unis] ; Kimberly Dodd [États-Unis] ; Mike Flint [États-Unis] ; Aridth Gibbons [États-Unis] ; Christin Goodman [États-Unis] ; John Klena [États-Unis] ; Laura Mcmullan [États-Unis] ; Laura Morgan [États-Unis] ; Brandy Russell [États-Unis] ; Johanna Salzer [États-Unis] ; Angela Sanchez [États-Unis] ; David Wang [États-Unis] ; Irwin Jungreis [États-Unis] ; Christopher Tomkins-Tinch [États-Unis] ; Andrey Kislyuk [États-Unis] ; Michael F. Lin [États-Unis] ; Sinead Chapman [États-Unis] ; Bronwyn Macinnis [États-Unis] ; Ashley Matthews [États-Unis] ; James Bochicchio [États-Unis] ; Lisa E. Hensley [États-Unis] ; Jens H. Kuhn [États-Unis] ; Chad Nusbaum [États-Unis] ; John S. Schieffelin [États-Unis] ; Bruce W. Birren [États-Unis] ; Marc Forget [Belgique] ; Stuart T. Nichol [États-Unis] ; Gustavo F. Palacios [États-Unis] ; Daouda Ndiaye [Sénégal] ; Christian Happi [Nigeria] ; Sahr M. Gevao [Sierra Leone] ; Mohamed A. Vandi [Sierra Leone] ; Brima Kargbo [Sierra Leone] ; Edward C. Holmes [Australie] ; Trevor Bedford [États-Unis] ; Andreas Gnirke [États-Unis] ; Ute Ströher [États-Unis] ; Andrew Rambaut [Royaume-Uni, États-Unis] ; Robert F. Garry [États-Unis] ; Pardis C. Sabeti [États-Unis]Source :
- Cell [ 0092-8674 ] ; 2015.
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.
Url:
DOI: 10.1016/j.cell.2015.06.007
PubMed: 26091036
PubMed Central: 4503805
Affiliations:
- Australie, Belgique, Nigeria, Royaume-Uni, Sierra Leone, Sénégal, États-Unis
- Californie, Géorgie (États-Unis), Louisiane, Maryland, Massachusetts, Vienne (Autriche), Washington (État), Écosse
- Cambridge (Massachusetts), Vienne (Autriche), Édimbourg
- Université Harvard, Université d'Édimbourg
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Moses</name><affiliation wicri:level="2"><nlm:aff id="aff9">Tulane University, 1430 Tulane Avenue, SL-38, New Orleans, LA 70112, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Tulane University, 1430 Tulane Avenue, SL-38, New Orleans, LA 70112</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Jiang, Pan Pan" sort="Jiang, Pan Pan" uniqKey="Jiang P" first="Pan-Pan" last="Jiang">Pan-Pan Jiang</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3">Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Harvard University, 52 Oxford Street, Cambridge, MA 02138</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Lin, Aaron E" sort="Lin, Aaron E" uniqKey="Lin A" first="Aaron E." last="Lin">Aaron E. 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Schaffner</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3">Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Harvard University, 52 Oxford Street, Cambridge, MA 02138</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Bird, Brian" sort="Bird, Brian" uniqKey="Bird B" first="Brian" last="Bird">Brian Bird</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Towner, Jonathan" sort="Towner, Jonathan" uniqKey="Towner J" first="Jonathan" last="Towner">Jonathan Towner</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Mamoh, Mambu" sort="Mamoh, Mambu" uniqKey="Mamoh M" first="Mambu" last="Mamoh">Mambu Mamoh</name><affiliation wicri:level="1"><nlm:aff id="aff4">Kenema Government Hospital, Kenema, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>Kenema Government Hospital, Kenema</wicri:regionArea><wicri:noRegion>Kenema</wicri:noRegion></affiliation></author><author><name sortKey="Gbakie, Michael" sort="Gbakie, Michael" uniqKey="Gbakie M" first="Michael" last="Gbakie">Michael Gbakie</name><affiliation wicri:level="1"><nlm:aff id="aff4">Kenema Government Hospital, Kenema, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>Kenema Government Hospital, Kenema</wicri:regionArea><wicri:noRegion>Kenema</wicri:noRegion></affiliation></author><author><name sortKey="Kanneh, Lansana" sort="Kanneh, Lansana" uniqKey="Kanneh L" first="Lansana" last="Kanneh">Lansana Kanneh</name><affiliation wicri:level="1"><nlm:aff id="aff4">Kenema Government Hospital, Kenema, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>Kenema Government Hospital, Kenema</wicri:regionArea><wicri:noRegion>Kenema</wicri:noRegion></affiliation></author><author><name sortKey="Kargbo, David" sort="Kargbo, David" uniqKey="Kargbo D" first="David" last="Kargbo">David Kargbo</name><affiliation wicri:level="1"><nlm:aff id="aff4">Kenema Government Hospital, Kenema, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>Kenema Government Hospital, Kenema</wicri:regionArea><wicri:noRegion>Kenema</wicri:noRegion></affiliation></author><author><name sortKey="Massally, James L B" sort="Massally, James L B" uniqKey="Massally J" first="James L. B." last="Massally">James L. B. Massally</name><affiliation wicri:level="1"><nlm:aff id="aff4">Kenema Government Hospital, Kenema, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>Kenema Government Hospital, Kenema</wicri:regionArea><wicri:noRegion>Kenema</wicri:noRegion></affiliation></author><author><name sortKey="Kamara, Fatima K" sort="Kamara, Fatima K" uniqKey="Kamara F" first="Fatima K." last="Kamara">Fatima K. Kamara</name><affiliation wicri:level="1"><nlm:aff id="aff4">Kenema Government Hospital, Kenema, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>Kenema Government Hospital, Kenema</wicri:regionArea><wicri:noRegion>Kenema</wicri:noRegion></affiliation></author><author><name sortKey="Konuwa, Edwin" sort="Konuwa, Edwin" uniqKey="Konuwa E" first="Edwin" last="Konuwa">Edwin Konuwa</name><affiliation wicri:level="1"><nlm:aff id="aff4">Kenema Government Hospital, Kenema, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>Kenema Government Hospital, Kenema</wicri:regionArea><wicri:noRegion>Kenema</wicri:noRegion></affiliation></author><author><name sortKey="Sellu, Josephine" sort="Sellu, Josephine" uniqKey="Sellu J" first="Josephine" last="Sellu">Josephine Sellu</name><affiliation wicri:level="1"><nlm:aff id="aff4">Kenema Government Hospital, Kenema, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>Kenema Government Hospital, Kenema</wicri:regionArea><wicri:noRegion>Kenema</wicri:noRegion></affiliation></author><author><name sortKey="Jalloh, Abdul A" sort="Jalloh, Abdul A" uniqKey="Jalloh A" first="Abdul A." last="Jalloh">Abdul A. 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Erickson</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Sealy, Tara" sort="Sealy, Tara" uniqKey="Sealy T" first="Tara" last="Sealy">Tara Sealy</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Blau, Dianna" sort="Blau, Dianna" uniqKey="Blau D" first="Dianna" last="Blau">Dianna Blau</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Paddock, Christopher" sort="Paddock, Christopher" uniqKey="Paddock C" first="Christopher" last="Paddock">Christopher Paddock</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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, 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sort="Amman, Brian" uniqKey="Amman B" first="Brian" last="Amman">Brian Amman</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Basile, Jane" sort="Basile, Jane" uniqKey="Basile J" first="Jane" last="Basile">Jane Basile</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Bearden, Scott" sort="Bearden, Scott" uniqKey="Bearden S" first="Scott" last="Bearden">Scott Bearden</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Belser, Jessica" sort="Belser, Jessica" uniqKey="Belser J" first="Jessica" last="Belser">Jessica Belser</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers 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last="Chakrabarti">Ayan Chakrabarti</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Dodd, Kimberly" sort="Dodd, Kimberly" uniqKey="Dodd K" first="Kimberly" last="Dodd">Kimberly Dodd</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Flint, Mike" sort="Flint, Mike" uniqKey="Flint M" first="Mike" last="Flint">Mike Flint</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Gibbons, Aridth" sort="Gibbons, Aridth" uniqKey="Gibbons A" first="Aridth" last="Gibbons">Aridth Gibbons</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, 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Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Russell, Brandy" sort="Russell, Brandy" uniqKey="Russell B" first="Brandy" last="Russell">Brandy Russell</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Salzer, Johanna" sort="Salzer, Johanna" uniqKey="Salzer J" first="Johanna" last="Salzer">Johanna Salzer</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Sanchez, Angela" sort="Sanchez, Angela" uniqKey="Sanchez A" first="Angela" last="Sanchez">Angela Sanchez</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Wang, David" sort="Wang, David" uniqKey="Wang D" first="David" last="Wang">David Wang</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Jungreis, Irwin" sort="Jungreis, Irwin" uniqKey="Jungreis I" first="Irwin" last="Jungreis">Irwin Jungreis</name><affiliation wicri:level="2"><nlm:aff id="aff7">Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Tomkins Tinch, Christopher" sort="Tomkins Tinch, Christopher" uniqKey="Tomkins Tinch C" first="Christopher" last="Tomkins-Tinch">Christopher Tomkins-Tinch</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Kislyuk, Andrey" sort="Kislyuk, Andrey" uniqKey="Kislyuk A" first="Andrey" last="Kislyuk">Andrey Kislyuk</name><affiliation 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Lin</name><affiliation wicri:level="2"><nlm:aff id="aff10">DNAnexus, 1975 West El Camino Real, Suite 101, Mountain View, CA 94040, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>DNAnexus, 1975 West El Camino Real, Suite 101, Mountain View, CA 94040</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Chapman, Sinead" sort="Chapman, Sinead" uniqKey="Chapman S" first="Sinead" last="Chapman">Sinead Chapman</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Macinnis, Bronwyn" sort="Macinnis, Bronwyn" uniqKey="Macinnis B" first="Bronwyn" last="Macinnis">Bronwyn Macinnis</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Matthews, Ashley" sort="Matthews, Ashley" uniqKey="Matthews A" first="Ashley" last="Matthews">Ashley Matthews</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3">Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Harvard University, 52 Oxford Street, Cambridge, MA 02138</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Bochicchio, James" sort="Bochicchio, James" uniqKey="Bochicchio J" first="James" last="Bochicchio">James Bochicchio</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Hensley, Lisa E" sort="Hensley, Lisa E" uniqKey="Hensley L" first="Lisa E." last="Hensley">Lisa E. Hensley</name><affiliation wicri:level="2"><nlm:aff id="aff11">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Kuhn, Jens H" sort="Kuhn, Jens H" uniqKey="Kuhn J" first="Jens H." last="Kuhn">Jens H. 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Schieffelin</name><affiliation wicri:level="2"><nlm:aff id="aff9">Tulane University, 1430 Tulane Avenue, SL-38, New Orleans, LA 70112, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Tulane University, 1430 Tulane Avenue, SL-38, New Orleans, LA 70112</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Birren, Bruce W" sort="Birren, Bruce W" uniqKey="Birren B" first="Bruce W." last="Birren">Bruce W. 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Nichol</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Palacios, Gustavo F" sort="Palacios, Gustavo F" uniqKey="Palacios G" first="Gustavo F." last="Palacios">Gustavo F. Palacios</name><affiliation wicri:level="2"><nlm:aff id="aff8">US Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>US Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Ndiaye, Daouda" sort="Ndiaye, Daouda" uniqKey="Ndiaye D" first="Daouda" last="Ndiaye">Daouda Ndiaye</name><affiliation wicri:level="1"><nlm:aff id="aff13">Université Cheikh Anta Diop, BP 5005, Dakar, Sénégal</nlm:aff><country xml:lang="fr">Sénégal</country><wicri:regionArea>Université Cheikh Anta Diop, BP 5005, Dakar</wicri:regionArea><wicri:noRegion>Dakar</wicri:noRegion></affiliation></author><author><name sortKey="Happi, Christian" sort="Happi, Christian" uniqKey="Happi C" first="Christian" last="Happi">Christian Happi</name><affiliation wicri:level="1"><nlm:aff id="aff14">Redeemers University Nigeria, KM 46 Lagos-Ibadan Expressway, Redemption City, Ogun State, Nigeria</nlm:aff><country xml:lang="fr">Nigeria</country><wicri:regionArea>Redeemers University Nigeria, KM 46 Lagos-Ibadan Expressway, Redemption City, Ogun State</wicri:regionArea><wicri:noRegion>Ogun State</wicri:noRegion></affiliation></author><author><name sortKey="Gevao, Sahr M" sort="Gevao, Sahr M" uniqKey="Gevao S" first="Sahr M." last="Gevao">Sahr M. Gevao</name><affiliation wicri:level="1"><nlm:aff id="aff15">University of Sierra Leone, A.J. Momoh St, Tower Hill, Freetown, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>University of Sierra Leone, A.J. Momoh St, Tower Hill, Freetown</wicri:regionArea><wicri:noRegion>Freetown</wicri:noRegion></affiliation></author><author><name sortKey="Vandi, Mohamed A" sort="Vandi, Mohamed A" uniqKey="Vandi M" first="Mohamed A." last="Vandi">Mohamed A. Vandi</name><affiliation wicri:level="1"><nlm:aff id="aff16">Sierra Leone Ministry of Health and Sanitation, Youyi Building, Freetown, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>Sierra Leone Ministry of Health and Sanitation, Youyi Building, Freetown</wicri:regionArea><wicri:noRegion>Freetown</wicri:noRegion></affiliation></author><author><name sortKey="Kargbo, Brima" sort="Kargbo, Brima" uniqKey="Kargbo B" first="Brima" last="Kargbo">Brima Kargbo</name><affiliation wicri:level="1"><nlm:aff id="aff16">Sierra Leone Ministry of Health and Sanitation, Youyi Building, Freetown, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>Sierra Leone Ministry of Health and Sanitation, Youyi Building, Freetown</wicri:regionArea><wicri:noRegion>Freetown</wicri:noRegion></affiliation></author><author><name sortKey="Holmes, Edward C" sort="Holmes, Edward C" uniqKey="Holmes E" first="Edward C." last="Holmes">Edward C. Holmes</name><affiliation wicri:level="1"><nlm:aff id="aff17">University of Sydney, Johns Hopkins Drive, Camperdown NSW 2050, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Sydney, Johns Hopkins Drive, Camperdown NSW 2050</wicri:regionArea><wicri:noRegion>Camperdown NSW 2050</wicri:noRegion></affiliation></author><author><name sortKey="Bedford, Trevor" sort="Bedford, Trevor" uniqKey="Bedford T" first="Trevor" last="Bedford">Trevor Bedford</name><affiliation wicri:level="2"><nlm:aff id="aff18">Fred Hutchinson Cancer Research Center, 110 Fairview Avenue North, Seattle, WA 98109, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Fred Hutchinson Cancer Research Center, 110 Fairview Avenue North, Seattle, WA 98109</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Gnirke, Andreas" sort="Gnirke, Andreas" uniqKey="Gnirke A" first="Andreas" last="Gnirke">Andreas Gnirke</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Stroher, Ute" sort="Stroher, Ute" uniqKey="Stroher U" first="Ute" last="Ströher">Ute Ströher</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Rambaut, Andrew" sort="Rambaut, Andrew" uniqKey="Rambaut A" first="Andrew" last="Rambaut">Andrew Rambaut</name><affiliation wicri:level="4"><nlm:aff id="aff2">Institute of Evolutionary Biology, Ashworth Laboratories, University of Edinburgh, Edinburgh EH9 3FL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Evolutionary Biology, Ashworth Laboratories, University of Edinburgh, Edinburgh EH9 3FL</wicri:regionArea><orgName type="university">Université d'Édimbourg</orgName><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff19">Centre for Immunology, Infection and Evolution, University of Edinburgh, Ashworth Laboratories, Edinburgh EH9 3FL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Immunology, Infection and Evolution, University of Edinburgh, Ashworth Laboratories, Edinburgh EH9 3FL</wicri:regionArea><orgName type="university">Université d'Édimbourg</orgName><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff20">Fogarty International Center, National Institutes of Health, 31 Center Drive, MSC 2220 Bethesda, MD 20892, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Fogarty International Center, National Institutes of Health, 31 Center Drive, MSC 2220 Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Garry, Robert F" sort="Garry, Robert F" uniqKey="Garry R" first="Robert F." last="Garry">Robert F. Garry</name><affiliation wicri:level="2"><nlm:aff id="aff9">Tulane University, 1430 Tulane Avenue, SL-38, New Orleans, LA 70112, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Tulane University, 1430 Tulane Avenue, SL-38, New Orleans, LA 70112</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Sabeti, Pardis C" sort="Sabeti, Pardis C" uniqKey="Sabeti P" first="Pardis C." last="Sabeti">Pardis C. Sabeti</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3">Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Harvard University, 52 Oxford Street, Cambridge, MA 02138</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26091036</idno><idno type="pmc">4503805</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4503805</idno><idno type="RBID">PMC:4503805</idno><idno type="doi">10.1016/j.cell.2015.06.007</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000351</idno><idno type="wicri:Area/Pmc/Curation">000351</idno><idno type="wicri:Area/Pmc/Checkpoint">000141</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone</title><author><name sortKey="Park, Daniel J" sort="Park, Daniel J" uniqKey="Park D" first="Daniel J." last="Park">Daniel J. Park</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Dudas, Gytis" sort="Dudas, Gytis" uniqKey="Dudas G" first="Gytis" last="Dudas">Gytis Dudas</name><affiliation wicri:level="4"><nlm:aff id="aff2">Institute of Evolutionary Biology, Ashworth Laboratories, University of Edinburgh, Edinburgh EH9 3FL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Evolutionary Biology, Ashworth Laboratories, University of Edinburgh, Edinburgh EH9 3FL</wicri:regionArea><orgName type="university">Université d'Édimbourg</orgName><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region></placeName></affiliation></author><author><name sortKey="Wohl, Shirlee" sort="Wohl, Shirlee" uniqKey="Wohl S" first="Shirlee" last="Wohl">Shirlee Wohl</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3">Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Harvard University, 52 Oxford Street, Cambridge, MA 02138</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Goba, Augustine" sort="Goba, Augustine" uniqKey="Goba A" first="Augustine" last="Goba">Augustine Goba</name><affiliation wicri:level="1"><nlm:aff id="aff4">Kenema Government Hospital, Kenema, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>Kenema Government Hospital, Kenema</wicri:regionArea><wicri:noRegion>Kenema</wicri:noRegion></affiliation></author><author><name sortKey="Whitmer, Shannon L M" sort="Whitmer, Shannon L M" uniqKey="Whitmer S" first="Shannon L. M." last="Whitmer">Shannon L. M. Whitmer</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Andersen, Kristian G" sort="Andersen, Kristian G" uniqKey="Andersen K" first="Kristian G." last="Andersen">Kristian G. Andersen</name><affiliation wicri:level="2"><nlm:aff id="aff6">Scripps Translational Science Institute, The Scripps Research Institute, 3344 N Torrey Pines Court, La Jolla, CA 92037, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Scripps Translational Science Institute, The Scripps Research Institute, 3344 N Torrey Pines Court, La Jolla, CA 92037</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Sealfon, Rachel S" sort="Sealfon, Rachel S" uniqKey="Sealfon R" first="Rachel S." last="Sealfon">Rachel S. Sealfon</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff7">Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Ladner, Jason T" sort="Ladner, Jason T" uniqKey="Ladner J" first="Jason T." last="Ladner">Jason T. Ladner</name><affiliation wicri:level="2"><nlm:aff id="aff8">US Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>US Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Kugelman, Jeffrey R" sort="Kugelman, Jeffrey R" uniqKey="Kugelman J" first="Jeffrey R." last="Kugelman">Jeffrey R. Kugelman</name><affiliation wicri:level="2"><nlm:aff id="aff8">US Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>US Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Matranga, Christian B" sort="Matranga, Christian B" uniqKey="Matranga C" first="Christian B." last="Matranga">Christian B. Matranga</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Winnicki, Sarah M" sort="Winnicki, Sarah M" uniqKey="Winnicki S" first="Sarah M." last="Winnicki">Sarah M. Winnicki</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3">Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Harvard University, 52 Oxford Street, Cambridge, MA 02138</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Qu, James" sort="Qu, James" uniqKey="Qu J" first="James" last="Qu">James Qu</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Gire, Stephen K" sort="Gire, Stephen K" uniqKey="Gire S" first="Stephen K." last="Gire">Stephen K. Gire</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3">Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Harvard University, 52 Oxford Street, Cambridge, MA 02138</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Gladden Young, Adrianne" sort="Gladden Young, Adrianne" uniqKey="Gladden Young A" first="Adrianne" last="Gladden-Young">Adrianne Gladden-Young</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Jalloh, Simbirie" sort="Jalloh, Simbirie" uniqKey="Jalloh S" first="Simbirie" last="Jalloh">Simbirie Jalloh</name><affiliation wicri:level="1"><nlm:aff id="aff4">Kenema Government Hospital, Kenema, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>Kenema Government Hospital, Kenema</wicri:regionArea><wicri:noRegion>Kenema</wicri:noRegion></affiliation></author><author><name sortKey="Nosamiefan, Dolo" sort="Nosamiefan, Dolo" uniqKey="Nosamiefan D" first="Dolo" last="Nosamiefan">Dolo Nosamiefan</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Yozwiak, Nathan L" sort="Yozwiak, Nathan L" uniqKey="Yozwiak N" first="Nathan L." last="Yozwiak">Nathan L. Yozwiak</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3">Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Harvard University, 52 Oxford Street, Cambridge, MA 02138</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Moses, Lina M" sort="Moses, Lina M" uniqKey="Moses L" first="Lina M." last="Moses">Lina M. Moses</name><affiliation wicri:level="2"><nlm:aff id="aff9">Tulane University, 1430 Tulane Avenue, SL-38, New Orleans, LA 70112, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Tulane University, 1430 Tulane Avenue, SL-38, New Orleans, LA 70112</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Jiang, Pan Pan" sort="Jiang, Pan Pan" uniqKey="Jiang P" first="Pan-Pan" last="Jiang">Pan-Pan Jiang</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3">Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Harvard University, 52 Oxford Street, Cambridge, MA 02138</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Lin, Aaron E" sort="Lin, Aaron E" uniqKey="Lin A" first="Aaron E." last="Lin">Aaron E. Lin</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3">Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Harvard University, 52 Oxford Street, Cambridge, MA 02138</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Schaffner, Stephen F" sort="Schaffner, Stephen F" uniqKey="Schaffner S" first="Stephen F." last="Schaffner">Stephen F. Schaffner</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3">Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Harvard University, 52 Oxford Street, Cambridge, MA 02138</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Bird, Brian" sort="Bird, Brian" uniqKey="Bird B" first="Brian" last="Bird">Brian Bird</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Towner, Jonathan" sort="Towner, Jonathan" uniqKey="Towner J" first="Jonathan" last="Towner">Jonathan Towner</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Mamoh, Mambu" sort="Mamoh, Mambu" uniqKey="Mamoh M" first="Mambu" last="Mamoh">Mambu Mamoh</name><affiliation wicri:level="1"><nlm:aff id="aff4">Kenema Government Hospital, Kenema, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>Kenema Government Hospital, Kenema</wicri:regionArea><wicri:noRegion>Kenema</wicri:noRegion></affiliation></author><author><name sortKey="Gbakie, Michael" sort="Gbakie, Michael" uniqKey="Gbakie M" first="Michael" last="Gbakie">Michael Gbakie</name><affiliation wicri:level="1"><nlm:aff id="aff4">Kenema Government Hospital, Kenema, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>Kenema Government Hospital, Kenema</wicri:regionArea><wicri:noRegion>Kenema</wicri:noRegion></affiliation></author><author><name sortKey="Kanneh, Lansana" sort="Kanneh, Lansana" uniqKey="Kanneh L" first="Lansana" last="Kanneh">Lansana Kanneh</name><affiliation wicri:level="1"><nlm:aff id="aff4">Kenema Government Hospital, Kenema, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>Kenema Government Hospital, Kenema</wicri:regionArea><wicri:noRegion>Kenema</wicri:noRegion></affiliation></author><author><name sortKey="Kargbo, David" sort="Kargbo, David" uniqKey="Kargbo D" first="David" last="Kargbo">David Kargbo</name><affiliation wicri:level="1"><nlm:aff id="aff4">Kenema Government Hospital, Kenema, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>Kenema Government Hospital, Kenema</wicri:regionArea><wicri:noRegion>Kenema</wicri:noRegion></affiliation></author><author><name sortKey="Massally, James L B" sort="Massally, James L B" uniqKey="Massally J" first="James L. B." last="Massally">James L. B. Massally</name><affiliation wicri:level="1"><nlm:aff id="aff4">Kenema Government Hospital, Kenema, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>Kenema Government Hospital, Kenema</wicri:regionArea><wicri:noRegion>Kenema</wicri:noRegion></affiliation></author><author><name sortKey="Kamara, Fatima K" sort="Kamara, Fatima K" uniqKey="Kamara F" first="Fatima K." last="Kamara">Fatima K. Kamara</name><affiliation wicri:level="1"><nlm:aff id="aff4">Kenema Government Hospital, Kenema, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>Kenema Government Hospital, Kenema</wicri:regionArea><wicri:noRegion>Kenema</wicri:noRegion></affiliation></author><author><name sortKey="Konuwa, Edwin" sort="Konuwa, Edwin" uniqKey="Konuwa E" first="Edwin" last="Konuwa">Edwin Konuwa</name><affiliation wicri:level="1"><nlm:aff id="aff4">Kenema Government Hospital, Kenema, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>Kenema Government Hospital, Kenema</wicri:regionArea><wicri:noRegion>Kenema</wicri:noRegion></affiliation></author><author><name sortKey="Sellu, Josephine" sort="Sellu, Josephine" uniqKey="Sellu J" first="Josephine" last="Sellu">Josephine Sellu</name><affiliation wicri:level="1"><nlm:aff id="aff4">Kenema Government Hospital, Kenema, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>Kenema Government Hospital, Kenema</wicri:regionArea><wicri:noRegion>Kenema</wicri:noRegion></affiliation></author><author><name sortKey="Jalloh, Abdul A" sort="Jalloh, Abdul A" uniqKey="Jalloh A" first="Abdul A." last="Jalloh">Abdul A. 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Erickson</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Sealy, Tara" sort="Sealy, Tara" uniqKey="Sealy T" first="Tara" last="Sealy">Tara Sealy</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Blau, Dianna" sort="Blau, Dianna" uniqKey="Blau D" first="Dianna" last="Blau">Dianna Blau</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>National Center for Emerging and 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sort="Amman, Brian" uniqKey="Amman B" first="Brian" last="Amman">Brian Amman</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Basile, Jane" sort="Basile, Jane" uniqKey="Basile J" first="Jane" last="Basile">Jane Basile</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Bearden, Scott" sort="Bearden, Scott" uniqKey="Bearden S" first="Scott" last="Bearden">Scott Bearden</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Belser, Jessica" sort="Belser, Jessica" uniqKey="Belser J" first="Jessica" last="Belser">Jessica Belser</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>National Center for Emerging and Zoonotic Infectious Diseases and National Center for Immunization and Respiratory Diseases, Centers 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and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop-G14, Atlanta, GA 30333, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Flint, Mike" sort="Flint, Mike" uniqKey="Flint M" first="Mike" last="Flint">Mike Flint</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Gibbons, Aridth" sort="Gibbons, Aridth" uniqKey="Gibbons A" first="Aridth" last="Gibbons">Aridth Gibbons</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Goodman, Christin" sort="Goodman, Christin" uniqKey="Goodman C" first="Christin" last="Goodman">Christin Goodman</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Klena, John" sort="Klena, John" uniqKey="Klena J" first="John" last="Klena">John Klena</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Mcmullan, Laura" sort="Mcmullan, Laura" uniqKey="Mcmullan L" first="Laura" last="Mcmullan">Laura Mcmullan</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Morgan, Laura" sort="Morgan, Laura" uniqKey="Morgan L" first="Laura" last="Morgan">Laura Morgan</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Russell, Brandy" sort="Russell, Brandy" uniqKey="Russell B" first="Brandy" last="Russell">Brandy Russell</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Salzer, Johanna" sort="Salzer, Johanna" uniqKey="Salzer J" first="Johanna" last="Salzer">Johanna Salzer</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Sanchez, Angela" sort="Sanchez, Angela" uniqKey="Sanchez A" first="Angela" last="Sanchez">Angela Sanchez</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Wang, David" sort="Wang, David" uniqKey="Wang D" first="David" last="Wang">David Wang</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Jungreis, Irwin" sort="Jungreis, Irwin" uniqKey="Jungreis I" first="Irwin" last="Jungreis">Irwin Jungreis</name><affiliation wicri:level="2"><nlm:aff id="aff7">Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Tomkins Tinch, Christopher" sort="Tomkins Tinch, Christopher" uniqKey="Tomkins Tinch C" first="Christopher" last="Tomkins-Tinch">Christopher Tomkins-Tinch</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Kislyuk, Andrey" sort="Kislyuk, Andrey" uniqKey="Kislyuk A" first="Andrey" last="Kislyuk">Andrey Kislyuk</name><affiliation wicri:level="2"><nlm:aff id="aff10">DNAnexus, 1975 West El Camino Real, Suite 101, Mountain View, CA 94040, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>DNAnexus, 1975 West El Camino Real, Suite 101, Mountain View, CA 94040</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Lin, Michael F" sort="Lin, Michael F" uniqKey="Lin M" first="Michael F." last="Lin">Michael F. Lin</name><affiliation wicri:level="2"><nlm:aff id="aff10">DNAnexus, 1975 West El Camino Real, Suite 101, Mountain View, CA 94040, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>DNAnexus, 1975 West El Camino Real, Suite 101, Mountain View, CA 94040</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Chapman, Sinead" sort="Chapman, Sinead" uniqKey="Chapman S" first="Sinead" last="Chapman">Sinead Chapman</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Macinnis, Bronwyn" sort="Macinnis, Bronwyn" uniqKey="Macinnis B" first="Bronwyn" last="Macinnis">Bronwyn Macinnis</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Matthews, Ashley" sort="Matthews, Ashley" uniqKey="Matthews A" first="Ashley" last="Matthews">Ashley Matthews</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3">Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Harvard University, 52 Oxford Street, Cambridge, MA 02138</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Bochicchio, James" sort="Bochicchio, James" uniqKey="Bochicchio J" first="James" last="Bochicchio">James Bochicchio</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Hensley, Lisa E" sort="Hensley, Lisa E" uniqKey="Hensley L" first="Lisa E." last="Hensley">Lisa E. Hensley</name><affiliation wicri:level="2"><nlm:aff id="aff11">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Kuhn, Jens H" sort="Kuhn, Jens H" uniqKey="Kuhn J" first="Jens H." last="Kuhn">Jens H. Kuhn</name><affiliation wicri:level="2"><nlm:aff id="aff11">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Nusbaum, Chad" sort="Nusbaum, Chad" uniqKey="Nusbaum C" first="Chad" last="Nusbaum">Chad Nusbaum</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Schieffelin, John S" sort="Schieffelin, John S" uniqKey="Schieffelin J" first="John S." last="Schieffelin">John S. Schieffelin</name><affiliation wicri:level="2"><nlm:aff id="aff9">Tulane University, 1430 Tulane Avenue, SL-38, New Orleans, LA 70112, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Tulane University, 1430 Tulane Avenue, SL-38, New Orleans, LA 70112</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Birren, Bruce W" sort="Birren, Bruce W" uniqKey="Birren B" first="Bruce W." last="Birren">Bruce W. Birren</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Forget, Marc" sort="Forget, Marc" uniqKey="Forget M" first="Marc" last="Forget">Marc Forget</name><affiliation wicri:level="3"><nlm:aff id="aff12">Médecins Sans Frontières, Rue de l’Arbre Bénit 46, 1050 Bruxelles, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Médecins Sans Frontières, Rue de l’Arbre Bénit 46, 1050 Bruxelles</wicri:regionArea><placeName><region type="land" nuts="2">Vienne (Autriche)</region><settlement type="city">Vienne (Autriche)</settlement></placeName></affiliation></author><author><name sortKey="Nichol, Stuart T" sort="Nichol, Stuart T" uniqKey="Nichol S" first="Stuart T." last="Nichol">Stuart T. Nichol</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Palacios, Gustavo F" sort="Palacios, Gustavo F" uniqKey="Palacios G" first="Gustavo F." last="Palacios">Gustavo F. Palacios</name><affiliation wicri:level="2"><nlm:aff id="aff8">US Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>US Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Ndiaye, Daouda" sort="Ndiaye, Daouda" uniqKey="Ndiaye D" first="Daouda" last="Ndiaye">Daouda Ndiaye</name><affiliation wicri:level="1"><nlm:aff id="aff13">Université Cheikh Anta Diop, BP 5005, Dakar, Sénégal</nlm:aff><country xml:lang="fr">Sénégal</country><wicri:regionArea>Université Cheikh Anta Diop, BP 5005, Dakar</wicri:regionArea><wicri:noRegion>Dakar</wicri:noRegion></affiliation></author><author><name sortKey="Happi, Christian" sort="Happi, Christian" uniqKey="Happi C" first="Christian" last="Happi">Christian Happi</name><affiliation wicri:level="1"><nlm:aff id="aff14">Redeemers University Nigeria, KM 46 Lagos-Ibadan Expressway, Redemption City, Ogun State, Nigeria</nlm:aff><country xml:lang="fr">Nigeria</country><wicri:regionArea>Redeemers University Nigeria, KM 46 Lagos-Ibadan Expressway, Redemption City, Ogun State</wicri:regionArea><wicri:noRegion>Ogun State</wicri:noRegion></affiliation></author><author><name sortKey="Gevao, Sahr M" sort="Gevao, Sahr M" uniqKey="Gevao S" first="Sahr M." last="Gevao">Sahr M. Gevao</name><affiliation wicri:level="1"><nlm:aff id="aff15">University of Sierra Leone, A.J. Momoh St, Tower Hill, Freetown, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>University of Sierra Leone, A.J. Momoh St, Tower Hill, Freetown</wicri:regionArea><wicri:noRegion>Freetown</wicri:noRegion></affiliation></author><author><name sortKey="Vandi, Mohamed A" sort="Vandi, Mohamed A" uniqKey="Vandi M" first="Mohamed A." last="Vandi">Mohamed A. Vandi</name><affiliation wicri:level="1"><nlm:aff id="aff16">Sierra Leone Ministry of Health and Sanitation, Youyi Building, Freetown, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>Sierra Leone Ministry of Health and Sanitation, Youyi Building, Freetown</wicri:regionArea><wicri:noRegion>Freetown</wicri:noRegion></affiliation></author><author><name sortKey="Kargbo, Brima" sort="Kargbo, Brima" uniqKey="Kargbo B" first="Brima" last="Kargbo">Brima Kargbo</name><affiliation wicri:level="1"><nlm:aff id="aff16">Sierra Leone Ministry of Health and Sanitation, Youyi Building, Freetown, Sierra Leone</nlm:aff><country xml:lang="fr">Sierra Leone</country><wicri:regionArea>Sierra Leone Ministry of Health and Sanitation, Youyi Building, Freetown</wicri:regionArea><wicri:noRegion>Freetown</wicri:noRegion></affiliation></author><author><name sortKey="Holmes, Edward C" sort="Holmes, Edward C" uniqKey="Holmes E" first="Edward C." last="Holmes">Edward C. Holmes</name><affiliation wicri:level="1"><nlm:aff id="aff17">University of Sydney, Johns Hopkins Drive, Camperdown NSW 2050, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Sydney, Johns Hopkins Drive, Camperdown NSW 2050</wicri:regionArea><wicri:noRegion>Camperdown NSW 2050</wicri:noRegion></affiliation></author><author><name sortKey="Bedford, Trevor" sort="Bedford, Trevor" uniqKey="Bedford T" first="Trevor" last="Bedford">Trevor Bedford</name><affiliation wicri:level="2"><nlm:aff id="aff18">Fred Hutchinson Cancer Research Center, 110 Fairview Avenue North, Seattle, WA 98109, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Fred Hutchinson Cancer Research Center, 110 Fairview Avenue North, Seattle, WA 98109</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Gnirke, Andreas" sort="Gnirke, Andreas" uniqKey="Gnirke A" first="Andreas" last="Gnirke">Andreas Gnirke</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Stroher, Ute" sort="Stroher, Ute" uniqKey="Stroher U" first="Ute" last="Ströher">Ute Ströher</name><affiliation wicri:level="2"><nlm:aff id="aff5">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</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Rambaut, Andrew" sort="Rambaut, Andrew" uniqKey="Rambaut A" first="Andrew" last="Rambaut">Andrew Rambaut</name><affiliation wicri:level="4"><nlm:aff id="aff2">Institute of Evolutionary Biology, Ashworth Laboratories, University of Edinburgh, Edinburgh EH9 3FL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Evolutionary Biology, Ashworth Laboratories, University of Edinburgh, Edinburgh EH9 3FL</wicri:regionArea><orgName type="university">Université d'Édimbourg</orgName><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff19">Centre for Immunology, Infection and Evolution, University of Edinburgh, Ashworth Laboratories, Edinburgh EH9 3FL, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Immunology, Infection and Evolution, University of Edinburgh, Ashworth Laboratories, Edinburgh EH9 3FL</wicri:regionArea><orgName type="university">Université d'Édimbourg</orgName><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff20">Fogarty International Center, National Institutes of Health, 31 Center Drive, MSC 2220 Bethesda, MD 20892, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Fogarty International Center, National Institutes of Health, 31 Center Drive, MSC 2220 Bethesda, MD 20892</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Garry, Robert F" sort="Garry, Robert F" uniqKey="Garry R" first="Robert F." last="Garry">Robert F. Garry</name><affiliation wicri:level="2"><nlm:aff id="aff9">Tulane University, 1430 Tulane Avenue, SL-38, New Orleans, LA 70112, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Tulane University, 1430 Tulane Avenue, SL-38, New Orleans, LA 70112</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Sabeti, Pardis C" sort="Sabeti, Pardis C" uniqKey="Sabeti P" first="Pardis C." last="Sabeti">Pardis C. Sabeti</name><affiliation wicri:level="2"><nlm:aff id="aff1">Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3">Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Harvard University, 52 Oxford Street, Cambridge, MA 02138</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author></analytic><series><title level="j">Cell</title><idno type="ISSN">0092-8674</idno><idno type="eISSN">1097-4172</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><p>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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Alizon, S" uniqKey="Alizon S">S. Alizon</name></author><author><name sortKey="Lion, S" uniqKey="Lion S">S. Lion</name></author><author><name sortKey="Murall, C L" uniqKey="Murall C">C.L. Murall</name></author><author><name sortKey="Abbate, J L" uniqKey="Abbate J">J.L. Abbate</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baize, S" uniqKey="Baize S">S. Baize</name></author><author><name sortKey="Pannetier, D" uniqKey="Pannetier D">D. Pannetier</name></author><author><name sortKey="Oestereich, L" uniqKey="Oestereich L">L. Oestereich</name></author><author><name sortKey="Rieger, T" uniqKey="Rieger T">T. Rieger</name></author><author><name sortKey="Koivogui, L" uniqKey="Koivogui L">L. 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ref-type="aff">1</xref><xref rid="aff3" ref-type="aff">3</xref></contrib><contrib contrib-type="author"><name><surname>Qu</surname><given-names>James</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Gire</surname><given-names>Stephen K.</given-names></name><xref rid="aff1" ref-type="aff">1</xref><xref rid="aff3" ref-type="aff">3</xref></contrib><contrib contrib-type="author"><name><surname>Gladden-Young</surname><given-names>Adrianne</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Jalloh</surname><given-names>Simbirie</given-names></name><xref rid="aff4" ref-type="aff">4</xref></contrib><contrib contrib-type="author"><name><surname>Nosamiefan</surname><given-names>Dolo</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Yozwiak</surname><given-names>Nathan L.</given-names></name><xref rid="aff1" ref-type="aff">1</xref><xref rid="aff3" ref-type="aff">3</xref></contrib><contrib contrib-type="author"><name><surname>Moses</surname><given-names>Lina M.</given-names></name><xref rid="aff9" ref-type="aff">9</xref></contrib><contrib contrib-type="author"><name><surname>Jiang</surname><given-names>Pan-Pan</given-names></name><xref rid="aff1" ref-type="aff">1</xref><xref rid="aff3" ref-type="aff">3</xref></contrib><contrib contrib-type="author"><name><surname>Lin</surname><given-names>Aaron E.</given-names></name><xref rid="aff1" ref-type="aff">1</xref><xref rid="aff3" ref-type="aff">3</xref></contrib><contrib contrib-type="author"><name><surname>Schaffner</surname><given-names>Stephen F.</given-names></name><xref rid="aff1" ref-type="aff">1</xref><xref rid="aff3" ref-type="aff">3</xref></contrib><contrib contrib-type="author"><name><surname>Bird</surname><given-names>Brian</given-names></name><xref rid="aff5" ref-type="aff">5</xref></contrib><contrib 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contrib-type="author"><name><surname>Morgan</surname><given-names>Laura</given-names></name><xref rid="aff5" ref-type="aff">5</xref></contrib><contrib contrib-type="author"><name><surname>Russell</surname><given-names>Brandy</given-names></name><xref rid="aff5" ref-type="aff">5</xref></contrib><contrib contrib-type="author"><name><surname>Salzer</surname><given-names>Johanna</given-names></name><xref rid="aff5" ref-type="aff">5</xref></contrib><contrib contrib-type="author"><name><surname>Sanchez</surname><given-names>Angela</given-names></name><xref rid="aff5" ref-type="aff">5</xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>David</given-names></name><xref rid="aff5" ref-type="aff">5</xref></contrib><contrib contrib-type="author"><name><surname>Jungreis</surname><given-names>Irwin</given-names></name><xref rid="aff7" ref-type="aff">7</xref></contrib><contrib 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contrib-type="author"><name><surname>Bochicchio</surname><given-names>James</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Hensley</surname><given-names>Lisa E.</given-names></name><xref rid="aff11" ref-type="aff">11</xref></contrib><contrib contrib-type="author"><name><surname>Kuhn</surname><given-names>Jens H.</given-names></name><xref rid="aff11" ref-type="aff">11</xref></contrib><contrib contrib-type="author"><name><surname>Nusbaum</surname><given-names>Chad</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Schieffelin</surname><given-names>John S.</given-names></name><xref rid="aff9" ref-type="aff">9</xref></contrib><contrib contrib-type="author"><name><surname>Birren</surname><given-names>Bruce W.</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Forget</surname><given-names>Marc</given-names></name><xref rid="aff12" ref-type="aff">12</xref></contrib><contrib contrib-type="author"><name><surname>Nichol</surname><given-names>Stuart T.</given-names></name><xref rid="aff5" ref-type="aff">5</xref></contrib><contrib contrib-type="author"><name><surname>Palacios</surname><given-names>Gustavo F.</given-names></name><xref rid="aff8" ref-type="aff">8</xref></contrib><contrib contrib-type="author"><name><surname>Ndiaye</surname><given-names>Daouda</given-names></name><xref rid="aff13" ref-type="aff">13</xref></contrib><contrib contrib-type="author"><name><surname>Happi</surname><given-names>Christian</given-names></name><xref rid="aff14" ref-type="aff">14</xref></contrib><contrib contrib-type="author"><name><surname>Gevao</surname><given-names>Sahr M.</given-names></name><xref rid="aff15" ref-type="aff">15</xref></contrib><contrib contrib-type="author"><name><surname>Vandi</surname><given-names>Mohamed A.</given-names></name><xref rid="aff16" ref-type="aff">16</xref></contrib><contrib contrib-type="author"><name><surname>Kargbo</surname><given-names>Brima</given-names></name><xref rid="aff16" ref-type="aff">16</xref></contrib><contrib contrib-type="author"><name><surname>Holmes</surname><given-names>Edward C.</given-names></name><xref rid="aff17" ref-type="aff">17</xref></contrib><contrib contrib-type="author"><name><surname>Bedford</surname><given-names>Trevor</given-names></name><xref rid="aff18" ref-type="aff">18</xref></contrib><contrib contrib-type="author"><name><surname>Gnirke</surname><given-names>Andreas</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Ströher</surname><given-names>Ute</given-names></name><xref rid="aff5" ref-type="aff">5</xref><xref rid="fn2" ref-type="fn">22</xref></contrib><contrib contrib-type="author"><name><surname>Rambaut</surname><given-names>Andrew</given-names></name><email>a.rambaut@ed.ac.uk</email><xref rid="aff2" ref-type="aff">2</xref><xref rid="aff19" ref-type="aff">19</xref><xref rid="aff20" ref-type="aff">20</xref><xref rid="fn2" ref-type="fn">22</xref><xref rid="cor2" ref-type="corresp">∗∗</xref></contrib><contrib contrib-type="author"><name><surname>Garry</surname><given-names>Robert F.</given-names></name><xref rid="aff9" ref-type="aff">9</xref><xref rid="fn2" ref-type="fn">22</xref></contrib><contrib contrib-type="author"><name><surname>Sabeti</surname><given-names>Pardis C.</given-names></name><email>pardis@broadinstitute.org</email><xref rid="aff1" ref-type="aff">1</xref><xref rid="aff3" ref-type="aff">3</xref><xref rid="fn2" ref-type="fn">22</xref><xref rid="cor3" ref-type="corresp">∗∗∗</xref></contrib></contrib-group><aff id="aff1"><label>1</label>Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA</aff><aff id="aff2"><label>2</label>Institute of Evolutionary Biology, Ashworth Laboratories, University of Edinburgh, Edinburgh EH9 3FL, UK</aff><aff id="aff3"><label>3</label>Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA</aff><aff id="aff4"><label>4</label>Kenema Government Hospital, Kenema, Sierra Leone</aff><aff id="aff5"><label>5</label>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</aff><aff id="aff6"><label>6</label>Scripps Translational Science Institute, The Scripps Research Institute, 3344 N Torrey Pines Court, La Jolla, CA 92037, USA</aff><aff id="aff7"><label>7</label>Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA</aff><aff id="aff8"><label>8</label>US Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA</aff><aff id="aff9"><label>9</label>Tulane University, 1430 Tulane Avenue, SL-38, New Orleans, LA 70112, USA</aff><aff id="aff10"><label>10</label>DNAnexus, 1975 West El Camino Real, Suite 101, Mountain View, CA 94040, USA</aff><aff id="aff11"><label>11</label>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</aff><aff id="aff12"><label>12</label>Médecins Sans Frontières, Rue de l’Arbre Bénit 46, 1050 Bruxelles, Belgium</aff><aff id="aff13"><label>13</label>Université Cheikh Anta Diop, BP 5005, Dakar, Sénégal</aff><aff id="aff14"><label>14</label>Redeemers University Nigeria, KM 46 Lagos-Ibadan Expressway, Redemption City, Ogun State, Nigeria</aff><aff id="aff15"><label>15</label>University of Sierra Leone, A.J. Momoh St, Tower Hill, Freetown, Sierra Leone</aff><aff id="aff16"><label>16</label>Sierra Leone Ministry of Health and Sanitation, Youyi Building, Freetown, Sierra Leone</aff><aff id="aff17"><label>17</label>University of Sydney, Johns Hopkins Drive, Camperdown NSW 2050, Australia</aff><aff id="aff18"><label>18</label>Fred Hutchinson Cancer Research Center, 110 Fairview Avenue North, Seattle, WA 98109, USA</aff><aff id="aff19"><label>19</label>Centre for Immunology, Infection and Evolution, University of Edinburgh, Ashworth Laboratories, Edinburgh EH9 3FL, UK</aff><aff id="aff20"><label>20</label>Fogarty International Center, National Institutes of Health, 31 Center Drive, MSC 2220 Bethesda, MD 20892, USA</aff><author-notes><corresp id="cor1"><label>∗</label>Corresponding author <email>dpark@broadinstitute.org</email></corresp><corresp id="cor2"><label>∗∗</label>Corresponding author <email>a.rambaut@ed.ac.uk</email></corresp><corresp id="cor3"><label>∗∗∗</label>Corresponding author <email>pardis@broadinstitute.org</email></corresp><fn id="fn1"><label>21</label><p>Co-first author</p></fn><fn id="fn2"><label>22</label><p>Co-senior author</p></fn></author-notes><pub-date pub-type="pmc-release"><day>18</day><month>6</month><year>2015</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><day>18</day><month>6</month><year>2015</year></pub-date><volume>161</volume><issue>7</issue><fpage>1516</fpage><lpage>1526</lpage><history><date date-type="received"><day>13</day><month>5</month><year>2015</year></date><date date-type="rev-recd"><day>26</day><month>5</month><year>2015</year></date><date date-type="accepted"><day>1</day><month>6</month><year>2015</year></date></history><permissions><copyright-statement>© 2015 The Authors</copyright-statement><copyright-year>2015</copyright-year><license license-type="CC BY-NC-ND" xlink:href="http://creativecommons.org/licenses/by-nc-nd/4.0/"><license-p>This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).</license-p></license></permissions><abstract><title>Summary</title><p>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.</p></abstract><abstract abstract-type="graphical"><title>Graphical Abstract</title><fig id="undfig1" position="anchor"><graphic xlink:href="fx1"></graphic></fig></abstract><abstract abstract-type="author-highlights"><title>Highlights</title><p><list list-type="simple"><list-item id="u0010"><label>•</label><p>In Sierra Leone, transmission has primarily been within-country, not between-country</p></list-item><list-item id="u0015"><label>•</label><p>Infectious doses are large enough for intrahost variants to transmit between hosts</p></list-item><list-item id="u0020"><label>•</label><p>A prolonged epidemic removes deleterious mutations from the viral population</p></list-item><list-item id="u0025"><label>•</label><p>There is preliminary evidence for human RNA editing effects on the Ebola genome</p></list-item></list></p></abstract><abstract abstract-type="teaser"><p>Ebola virus genomes from 232 patients sampled over 7 months in Sierra Leone were sequenced. Transmission of intrahost genetic variants suggests a sufficiently high infectious dose during transmission. The human host may have caused direct alterations to the Ebola virus genome.</p></abstract></article-meta><notes><p id="misc0010">Published: June 18, 2015</p></notes></front><floats-group><fig id="fig1"><label>Figure 1</label><caption><p>Within and between Country Genomic Relationships of Ebola Virus Makona</p><p>(A) Phylogenetic and temporal placement of recently sequenced Ebola virus (EBOV) within Sierra Leone. New EBOV genomes (232 genomes, dark blue), sampled from June 16 through December 26, 2014, provide a high-resolution view of the accumulated genetic diversity and fill in the missing ancestry between EBOV Makona genome data sets. The maximum clade credibility (MCC) tree was inferred using Bayesian evolutionary analysis by sampling trees (BEAST), with tips anchored to sampling date. Tips are labeled for EBOV from five non-African health-care workers (HCWs) infected in Sierra Leone and treated in Europe (sequenced by other groups, light green). Previously described nested EBOV Makona lineages SL1, SL2, and SL3 <xref rid="bib11" ref-type="bibr">Gire et al. (2014)</xref>, as well as a new lineage SL4, are labeled at their most-recent common ancestor (MRCA) nodes.</p><p>(B) Lack of EBOV Makona SL3 spread to Liberia or Mali. Shown is a median-joining haplotype network constructed from a coding-complete EBOV genome alignment including 340 EBOV Makona sequences. Each colored vertex represents a sampled viral haplotype, with colors indicating countries of origin. Colors are as in (A), with the exception that the distinction is no longer made between older (Gire) and newer (Park) Sierra Leonean data sets (both are now dark blue), and two additional countries are shown (Liberia in yellow, Mali in red). The size of the each vertex is relative to the number of sampled isolates. Hatch marks indicate the number of mutations along each edge.</p><p>See also <xref rid="figs1" ref-type="fig">Figures S1</xref> and <xref rid="figs2" ref-type="fig">S2</xref>.</p></caption><graphic xlink:href="gr1"></graphic></fig><fig id="fig2"><label>Figure 2</label><caption><p>Evidence for Host-to-Host Transmission of Multiple Ebola Virus Makona Genomes</p><p>(A) Certain intrahost variants (iSNVs) appear in samples throughout the 2013–2015 EVD epidemic, suggesting that iSNVs can be transmitted between patients. Variants shared between two or more samples are shown as rows of connected points; each row is a genomic position (ordered by position along the genome, top to bottom), and each point indicates the presence of the iSNV in a patient.</p><p>(B) Phylogenetic placement of derived alleles at genomic position 18,911 implies both repeated transmission within clades as well as some amount of recurrent mutation. Colored tips are sized according to frequency of iSNV at position 18,911. Tips with small black points are those with iSNV calls at any position; other tips represent samples with no iSNV calls. This figure shows only the portion of the tree relevant for this analysis; large branches with no SNPs or iSNVs at position 18,911 are not shown.</p><p>See also <xref rid="figs3" ref-type="fig">Figure S3</xref>.</p></caption><graphic xlink:href="gr2"></graphic></fig><fig id="fig3"><label>Figure 3</label><caption><p>Ebola Virus Evolution during a Prolonged EVD Epidemic</p><p>(A) Estimates of EBOV evolutionary rates at three timescales: decades (yellow, all known EVD outbreaks), months (blue, Baize + Gire + Park), and weeks (red: Baize + Gire).</p><p>(B) Purifying selection. We estimated nonsynonymous (red) and synonymous (blue) substitution rates on external (unique to an isolate, potential dead end) and internal (shared by multiple isolates, evidence of human-to-human transmission) branches. Nonsynonymous mutations accumulate faster on external branches than on internal branches. For synonymous mutations, the difference between external and internal branches is less pronounced.</p><p>(C) Enrichment for nonsynonymous mutations at shorter timescales. Intrahost (all variants that appear within a single host at less than 100% frequency); unique interhost (SNPs fixed in exactly one individual); shared interhost (SNPs fixed in two or more individuals); shared between EVD outbreaks (internal branch SNPs on a between-outbreak tree).</p><p>See also <xref rid="figs4" ref-type="fig">Figure S4</xref>.</p></caption><graphic xlink:href="gr3"></graphic></fig><fig id="fig4"><label>Figure 4</label><caption><p>Evidence for Host Effects on Ebola Virus Makona Evolution</p><p>(A) Nonsynonymous variants are enriched in the mucin-like domain of GP. Estimates of log(ω) (a.k.a., log(<italic>d</italic><sub>N</sub>/<italic>d</italic><sub>S</sub>)) per coding sequence within the Western African EVD outbreak (left) and between EVD outbreaks (right) demonstrate gene-specific patterns of natural selection.</p><p>(B) Nonsynonymous variants are enriched in B cell epitopes of GP. We calculated the fractions of nonsynonymous (NS) and synonymous (S) consensus SNPs and intrahost variants (iSNVs) within experimentally determined B cell epitopes (data from ViPR; <xref rid="bib22" ref-type="bibr">Pickett et al., 2012</xref>). Dotted line represents the fraction of GP amino acids in ViPR epitopes. Nonsynonymous SNPs (p = 0.004) and iSNVs (p = 0.037) in GP occur more frequently in epitopes than expected by chance (two-sided exact binomial test). Numbers indicate fraction of each variant type within GP epitope regions. Error bars represent binomial sampling intervals.</p><p>(C) Local enrichment of T-to-C mutations within GP B cell epitopes. We observed five sequences with short stretches (<200 nucleotides) of concentrated T-to-C mutations. Of these five sequences, two (shown here, samples 20141582 and G5119.1) contain stretches of T-to-C SNPs (blue points) within GP epitopes (light blue bars). Additionally, we observe a T-to-C mutation at amino acid position 485 (blue diamond) in three samples (one shown here, G4955.1), which is otherwise completely conserved among members of all ebolavirus species (<xref rid="bib20" ref-type="bibr">Olal et al., 2012</xref>).</p><p>(D) Genome-wide increase in T-to-C mutations. We observe more T-to-C transitions within the 2013–2015 outbreak than any other transition, after correcting for nucleotide content. Error bars represent binomial sampling intervals.</p><p>(E and F) Elevated T-to-C rates are genome wide but are limited to a subset of sequences. Accumulation of mutation increases linearly with time. However, some individual samples show more genetic distance than expected based on sample date. Samples with short stretches of T-to-C mutations (orange) show a significant enrichment of T-to-C mutations, as expected. Excluding these samples, the top 5% of samples by genetic distance (yellow) lack localized stretches but still show moderate enrichment of T-to-C mutations genome wide. The bottom 95% of samples (beige) show no enrichment of T-to-C mutations. Error bars represent binomial sampling intervals.</p></caption><graphic xlink:href="gr4"></graphic></fig><fig id="figs1"><label>Figure S1</label><caption><p>Phylogenetic and Temporal Context of Recent Tong et al. Samples, Related to <xref rid="fig1" ref-type="fig">Figure 1</xref></p><p>(A) 175 recently published Ebola virus Makona samples from Sierra Leone (<xref rid="bib26" ref-type="bibr">Tong et al., 2015</xref>) describe lineages that fall within the genetic diversity of our current dataset (MCC tree from BEAST, as in <xref rid="fig1" ref-type="fig">Figure 1</xref>). (B) They span a two month period (Sep 28 to Nov 11, 2014) that falls within the temporal sampling of our current data and shows a consistent evolutionary rate.</p></caption><graphic xlink:href="figs1"></graphic></fig><fig id="figs2"><label>Figure S2</label><caption><p>Tracing Historical Ebola Virus Makona Migrations from East to West, Related to <xref rid="fig1" ref-type="fig">Figure 1</xref></p><p>(A) Nine Ebola virus (EBOV) Makona genomes (right-hand most circles) from the Freetown area with four groups of apparently ancestral EBOV genomes (middle circles)). Groups of genetically identical genomes (circles) are related to each other by simple vertical relationships (arrows). Solid circles are shown on the date of the earliest sample in the group; the circle area is proportional to the number of samples containing viruses with that genome; arrows represent a set of non-homoplasic SNPs and point from ancestral to derived alleles. Here, “SL3” and “SL4” do not refer to entire clades, but to the viruses that exactly match the canonical SL3 and SL4 genomes with no further mutations. (B) Geographic mapping of one epidemiological route that may account for four of the nine Freetown viruses shown in (A). Groups of identical viruses are shown at their first observed location.</p></caption><graphic xlink:href="figs2"></graphic></fig><fig id="figs3"><label>Figure S3</label><caption><p>Ebola Virus Makona Intrahost Single-Nucleotide Variants, Related to <xref rid="fig2" ref-type="fig">Figure 2</xref></p><p>(A) Distribution of the number of iSNVs per sample. Replicate sequencing and iSNV calling was completed for 150 samples, of which 65 had no iSNV calls. Mean iSNVs per sample (including samples without iSNVs) = 2.04; mean iSNVs per sample (among samples with iSNVs) = 3.6. (B) Sample coverage by date shows the temporal distribution of samples containing Ebola virus (EBOV) genomes with and without iSNV calls. As expected, samples with iSNV calls have generally higher coverage. (C) Intermediate-frequency variants can persist over time with minimal genetic drift, as demonstrated by the iSNV at position 18,911. The existence of intermediate frequency (10%–30%) iSNVs in many different samples over time provides an argument against recurring mutations and may suggest a relatively wide transmission bottleneck between patients.</p></caption><graphic xlink:href="figs3"></graphic></fig><fig id="figs4"><label>Figure S4</label><caption><p>Increased Sampling Improves Evolutionary Rate Estimates, Related to <xref rid="fig3" ref-type="fig">Figure 3</xref></p><p>Rate estimates in the recent dataset (<xref rid="fig3" ref-type="fig">Figure 3</xref>A) have much tighter credible intervals due to the significantly greater amount of time (total coalescent branch length) compared to the initial outbreak.</p></caption><graphic xlink:href="figs4"></graphic></fig></floats-group></pmc><affiliations><list><country><li>Australie</li><li>Belgique</li><li>Nigeria</li><li>Royaume-Uni</li><li>Sierra Leone</li><li>Sénégal</li><li>États-Unis</li></country><region><li>Californie</li><li>Géorgie (États-Unis)</li><li>Louisiane</li><li>Maryland</li><li>Massachusetts</li><li>Vienne (Autriche)</li><li>Washington (État)</li><li>Écosse</li></region><settlement><li>Cambridge (Massachusetts)</li><li>Vienne (Autriche)</li><li>Édimbourg</li></settlement><orgName><li>Université Harvard</li><li>Université d'Édimbourg</li></orgName></list><tree><country name="États-Unis"><region name="Massachusetts"><name sortKey="Park, Daniel J" sort="Park, Daniel J" uniqKey="Park D" first="Daniel J." last="Park">Daniel J. 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Vandi</name><name sortKey="Yillah, Mohamed" sort="Yillah, Mohamed" uniqKey="Yillah M" first="Mohamed" last="Yillah">Mohamed Yillah</name></country><country name="Belgique"><region name="Vienne (Autriche)"><name sortKey="Forget, Marc" sort="Forget, Marc" uniqKey="Forget M" first="Marc" last="Forget">Marc Forget</name></region></country><country name="Sénégal"><noRegion><name sortKey="Ndiaye, Daouda" sort="Ndiaye, Daouda" uniqKey="Ndiaye D" first="Daouda" last="Ndiaye">Daouda Ndiaye</name></noRegion></country><country name="Nigeria"><noRegion><name sortKey="Happi, Christian" sort="Happi, Christian" uniqKey="Happi C" first="Christian" last="Happi">Christian Happi</name></noRegion></country><country name="Australie"><noRegion><name sortKey="Holmes, Edward C" sort="Holmes, Edward C" uniqKey="Holmes E" first="Edward C." last="Holmes">Edward C. Holmes</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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