Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone

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 patien...

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Veröffentlicht in:Cell 2015-06, Vol.161 (7), p.1516-1526
Hauptverfasser: Park, Daniel J., Dudas, Gytis, Wohl, Shirlee, Goba, Augustine, Whitmer, Shannon L.M., Andersen, Kristian G., Sealfon, Rachel S., Ladner, Jason T., Kugelman, Jeffrey R., Matranga, Christian B., Winnicki, Sarah M., Qu, James, Gire, Stephen K., Gladden-Young, Adrianne, Jalloh, Simbirie, Nosamiefan, Dolo, Yozwiak, Nathan L., Moses, Lina M., Jiang, Pan-Pan, Lin, Aaron E., Schaffner, Stephen F., Bird, Brian, Towner, Jonathan, Mamoh, Mambu, Gbakie, Michael, Kanneh, Lansana, Kargbo, David, Massally, James L.B., Kamara, Fatima K., Konuwa, Edwin, Sellu, Josephine, Jalloh, Abdul A., Mustapha, Ibrahim, Foday, Momoh, Yillah, Mohamed, Erickson, Bobbie R., Sealy, Tara, Blau, Dianna, Paddock, Christopher, Brault, Aaron, Amman, Brian, Basile, Jane, Bearden, Scott, Belser, Jessica, Bergeron, Eric, Campbell, Shelley, Chakrabarti, Ayan, Dodd, Kimberly, Flint, Mike, Gibbons, Aridth, Goodman, Christin, Klena, John, McMullan, Laura, Morgan, Laura, Russell, Brandy, Salzer, Johanna, Sanchez, Angela, Wang, David, Jungreis, Irwin, Tomkins-Tinch, Christopher, Kislyuk, Andrey, Lin, Michael F., Chapman, Sinead, MacInnis, Bronwyn, Matthews, Ashley, Bochicchio, James, Hensley, Lisa E., Kuhn, Jens H., Nusbaum, Chad, Schieffelin, John S., Birren, Bruce W., Forget, Marc, Nichol, Stuart T., Palacios, Gustavo F., Ndiaye, Daouda, Happi, Christian, Gevao, Sahr M., Vandi, Mohamed A., Kargbo, Brima, Holmes, Edward C., Bedford, Trevor, Gnirke, Andreas, Ströher, Ute, Rambaut, Andrew, Garry, Robert F., Sabeti, Pardis C.
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container_end_page 1526
container_issue 7
container_start_page 1516
container_title Cell
container_volume 161
creator Park, Daniel J.
Dudas, Gytis
Wohl, Shirlee
Goba, Augustine
Whitmer, Shannon L.M.
Andersen, Kristian G.
Sealfon, Rachel S.
Ladner, Jason T.
Kugelman, Jeffrey R.
Matranga, Christian B.
Winnicki, Sarah M.
Qu, James
Gire, Stephen K.
Gladden-Young, Adrianne
Jalloh, Simbirie
Nosamiefan, Dolo
Yozwiak, Nathan L.
Moses, Lina M.
Jiang, Pan-Pan
Lin, Aaron E.
Schaffner, Stephen F.
Bird, Brian
Towner, Jonathan
Mamoh, Mambu
Gbakie, Michael
Kanneh, Lansana
Kargbo, David
Massally, James L.B.
Kamara, Fatima K.
Konuwa, Edwin
Sellu, Josephine
Jalloh, Abdul A.
Mustapha, Ibrahim
Foday, Momoh
Yillah, Mohamed
Erickson, Bobbie R.
Sealy, Tara
Blau, Dianna
Paddock, Christopher
Brault, Aaron
Amman, Brian
Basile, Jane
Bearden, Scott
Belser, Jessica
Bergeron, Eric
Campbell, Shelley
Chakrabarti, Ayan
Dodd, Kimberly
Flint, Mike
Gibbons, Aridth
Goodman, Christin
Klena, John
McMullan, Laura
Morgan, Laura
Russell, Brandy
Salzer, Johanna
Sanchez, Angela
Wang, David
Jungreis, Irwin
Tomkins-Tinch, Christopher
Kislyuk, Andrey
Lin, Michael F.
Chapman, Sinead
MacInnis, Bronwyn
Matthews, Ashley
Bochicchio, James
Hensley, Lisa E.
Kuhn, Jens H.
Nusbaum, Chad
Schieffelin, John S.
Birren, Bruce W.
Forget, Marc
Nichol, Stuart T.
Palacios, Gustavo F.
Ndiaye, Daouda
Happi, Christian
Gevao, Sahr M.
Vandi, Mohamed A.
Kargbo, Brima
Holmes, Edward C.
Bedford, Trevor
Gnirke, Andreas
Ströher, Ute
Rambaut, Andrew
Garry, Robert F.
Sabeti, Pardis C.
description 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. [Display omitted] •In Sierra Leone, transmission has primarily been within-country, not between-country•Infectious doses are large enough for intrahost variants to transmit between hosts•A prolonged epidemic removes deleterious mutations from the viral population•There is preliminary evidence for human RNA editing effects on the Ebola genome 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.
doi_str_mv 10.1016/j.cell.2015.06.007
format Article
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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. [Display omitted] •In Sierra Leone, transmission has primarily been within-country, not between-country•Infectious doses are large enough for intrahost variants to transmit between hosts•A prolonged epidemic removes deleterious mutations from the viral population•There is preliminary evidence for human RNA editing effects on the Ebola genome 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.</description><identifier>ISSN: 0092-8674</identifier><identifier>ISSN: 1097-4172</identifier><identifier>EISSN: 1097-4172</identifier><identifier>DOI: 10.1016/j.cell.2015.06.007</identifier><identifier>PMID: 26091036</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Biological Evolution ; Disease Outbreaks ; disease transmission ; Ebolavirus ; Ebolavirus - classification ; Ebolavirus - genetics ; Ebolavirus - isolation &amp; purification ; evolution ; genetic variation ; genome ; Genome, Viral ; glycoproteins ; Hemorrhagic Fever, Ebola - epidemiology ; Hemorrhagic Fever, Ebola - transmission ; Hemorrhagic Fever, Ebola - virology ; Humans ; Mutation ; patients ; sequence analysis ; Sierra Leone ; Sierra Leone - epidemiology ; Specimen Handling ; viruses</subject><ispartof>Cell, 2015-06, Vol.161 (7), p.1516-1526</ispartof><rights>2015 The Authors</rights><rights>Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.</rights><rights>2015 The Authors 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c488t-e9b0d31433f4cb5ebf248e65cd0d16871fa022f36f8324c1a80814aa3c3c750f3</citedby><cites>FETCH-LOGICAL-c488t-e9b0d31433f4cb5ebf248e65cd0d16871fa022f36f8324c1a80814aa3c3c750f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S009286741500690X$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26091036$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Daniel J.</creatorcontrib><creatorcontrib>Dudas, Gytis</creatorcontrib><creatorcontrib>Wohl, Shirlee</creatorcontrib><creatorcontrib>Goba, Augustine</creatorcontrib><creatorcontrib>Whitmer, Shannon L.M.</creatorcontrib><creatorcontrib>Andersen, Kristian G.</creatorcontrib><creatorcontrib>Sealfon, Rachel S.</creatorcontrib><creatorcontrib>Ladner, Jason T.</creatorcontrib><creatorcontrib>Kugelman, Jeffrey R.</creatorcontrib><creatorcontrib>Matranga, Christian B.</creatorcontrib><creatorcontrib>Winnicki, Sarah M.</creatorcontrib><creatorcontrib>Qu, James</creatorcontrib><creatorcontrib>Gire, Stephen K.</creatorcontrib><creatorcontrib>Gladden-Young, Adrianne</creatorcontrib><creatorcontrib>Jalloh, Simbirie</creatorcontrib><creatorcontrib>Nosamiefan, Dolo</creatorcontrib><creatorcontrib>Yozwiak, Nathan L.</creatorcontrib><creatorcontrib>Moses, Lina M.</creatorcontrib><creatorcontrib>Jiang, Pan-Pan</creatorcontrib><creatorcontrib>Lin, Aaron E.</creatorcontrib><creatorcontrib>Schaffner, Stephen F.</creatorcontrib><creatorcontrib>Bird, Brian</creatorcontrib><creatorcontrib>Towner, Jonathan</creatorcontrib><creatorcontrib>Mamoh, Mambu</creatorcontrib><creatorcontrib>Gbakie, Michael</creatorcontrib><creatorcontrib>Kanneh, Lansana</creatorcontrib><creatorcontrib>Kargbo, David</creatorcontrib><creatorcontrib>Massally, James L.B.</creatorcontrib><creatorcontrib>Kamara, Fatima K.</creatorcontrib><creatorcontrib>Konuwa, Edwin</creatorcontrib><creatorcontrib>Sellu, Josephine</creatorcontrib><creatorcontrib>Jalloh, Abdul A.</creatorcontrib><creatorcontrib>Mustapha, Ibrahim</creatorcontrib><creatorcontrib>Foday, Momoh</creatorcontrib><creatorcontrib>Yillah, Mohamed</creatorcontrib><creatorcontrib>Erickson, Bobbie R.</creatorcontrib><creatorcontrib>Sealy, Tara</creatorcontrib><creatorcontrib>Blau, Dianna</creatorcontrib><creatorcontrib>Paddock, Christopher</creatorcontrib><creatorcontrib>Brault, Aaron</creatorcontrib><creatorcontrib>Amman, Brian</creatorcontrib><creatorcontrib>Basile, Jane</creatorcontrib><creatorcontrib>Bearden, Scott</creatorcontrib><creatorcontrib>Belser, Jessica</creatorcontrib><creatorcontrib>Bergeron, Eric</creatorcontrib><creatorcontrib>Campbell, Shelley</creatorcontrib><creatorcontrib>Chakrabarti, Ayan</creatorcontrib><creatorcontrib>Dodd, Kimberly</creatorcontrib><creatorcontrib>Flint, Mike</creatorcontrib><creatorcontrib>Gibbons, Aridth</creatorcontrib><creatorcontrib>Goodman, Christin</creatorcontrib><creatorcontrib>Klena, John</creatorcontrib><creatorcontrib>McMullan, Laura</creatorcontrib><creatorcontrib>Morgan, Laura</creatorcontrib><creatorcontrib>Russell, Brandy</creatorcontrib><creatorcontrib>Salzer, Johanna</creatorcontrib><creatorcontrib>Sanchez, Angela</creatorcontrib><creatorcontrib>Wang, David</creatorcontrib><creatorcontrib>Jungreis, Irwin</creatorcontrib><creatorcontrib>Tomkins-Tinch, Christopher</creatorcontrib><creatorcontrib>Kislyuk, Andrey</creatorcontrib><creatorcontrib>Lin, Michael F.</creatorcontrib><creatorcontrib>Chapman, Sinead</creatorcontrib><creatorcontrib>MacInnis, Bronwyn</creatorcontrib><creatorcontrib>Matthews, Ashley</creatorcontrib><creatorcontrib>Bochicchio, James</creatorcontrib><creatorcontrib>Hensley, Lisa E.</creatorcontrib><creatorcontrib>Kuhn, Jens H.</creatorcontrib><creatorcontrib>Nusbaum, Chad</creatorcontrib><creatorcontrib>Schieffelin, John S.</creatorcontrib><creatorcontrib>Birren, Bruce W.</creatorcontrib><creatorcontrib>Forget, Marc</creatorcontrib><creatorcontrib>Nichol, Stuart T.</creatorcontrib><creatorcontrib>Palacios, Gustavo F.</creatorcontrib><creatorcontrib>Ndiaye, Daouda</creatorcontrib><creatorcontrib>Happi, Christian</creatorcontrib><creatorcontrib>Gevao, Sahr M.</creatorcontrib><creatorcontrib>Vandi, Mohamed A.</creatorcontrib><creatorcontrib>Kargbo, Brima</creatorcontrib><creatorcontrib>Holmes, Edward C.</creatorcontrib><creatorcontrib>Bedford, Trevor</creatorcontrib><creatorcontrib>Gnirke, Andreas</creatorcontrib><creatorcontrib>Ströher, Ute</creatorcontrib><creatorcontrib>Rambaut, Andrew</creatorcontrib><creatorcontrib>Garry, Robert F.</creatorcontrib><creatorcontrib>Sabeti, Pardis C.</creatorcontrib><title>Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone</title><title>Cell</title><addtitle>Cell</addtitle><description>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. [Display omitted] •In Sierra Leone, transmission has primarily been within-country, not between-country•Infectious doses are large enough for intrahost variants to transmit between hosts•A prolonged epidemic removes deleterious mutations from the viral population•There is preliminary evidence for human RNA editing effects on the Ebola genome 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.</description><subject>Biological Evolution</subject><subject>Disease Outbreaks</subject><subject>disease transmission</subject><subject>Ebolavirus</subject><subject>Ebolavirus - classification</subject><subject>Ebolavirus - genetics</subject><subject>Ebolavirus - isolation &amp; purification</subject><subject>evolution</subject><subject>genetic variation</subject><subject>genome</subject><subject>Genome, Viral</subject><subject>glycoproteins</subject><subject>Hemorrhagic Fever, Ebola - epidemiology</subject><subject>Hemorrhagic Fever, Ebola - transmission</subject><subject>Hemorrhagic Fever, Ebola - virology</subject><subject>Humans</subject><subject>Mutation</subject><subject>patients</subject><subject>sequence analysis</subject><subject>Sierra Leone</subject><subject>Sierra Leone - epidemiology</subject><subject>Specimen Handling</subject><subject>viruses</subject><issn>0092-8674</issn><issn>1097-4172</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU-LFDEQxYMo7uzqF_AgOXrYbiv_utMggiyzKox42FXwFDLp6tkMPcmYdA_stzfDrIte9BSK_N6j6j1CXjGoGbDm7bZ2OI41B6ZqaGqA9glZMOjaSrKWPyULgI5XumnlGTnPeQsAWin1nJzxBjoGolmQH8t1HC397tOc6XLve9z5OMbN_SW9TTbknc_Zx3BJbejp8hDHeSoj7efkw4be4AED_RLDdJepD_TGY0qWrjAGfEGeDXbM-PLhvSDfrpe3V5-q1dePn68-rContZ4q7NbQCyaFGKRbK1wPXGpslOuhZ41u2WCB80E0gxZcOmY1aCatFU64VsEgLsj7k-9-Xu-wdximZEezT35n072J1pu_f4K_M5t4MFKB0KCKwZsHgxR_zpgnU44-JmsDxjkbXnLjnGkh_4uypgPOlBRdQfkJdSnmnHB43IiBOdZntuaoNMf6DDSm1FdEr_-85VHyu68CvDsBWBI9lLRNdh6Dw94ndJPpo_-X_y_Zq6xO</recordid><startdate>20150618</startdate><enddate>20150618</enddate><creator>Park, Daniel J.</creator><creator>Dudas, Gytis</creator><creator>Wohl, Shirlee</creator><creator>Goba, Augustine</creator><creator>Whitmer, 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Press</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20150618</creationdate><title>Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone</title><author>Park, Daniel J. ; Dudas, Gytis ; Wohl, Shirlee ; Goba, Augustine ; Whitmer, Shannon L.M. ; Andersen, Kristian G. ; Sealfon, Rachel S. ; Ladner, Jason T. ; Kugelman, Jeffrey R. ; Matranga, Christian B. ; Winnicki, Sarah M. ; Qu, James ; Gire, Stephen K. ; Gladden-Young, Adrianne ; Jalloh, Simbirie ; Nosamiefan, Dolo ; Yozwiak, Nathan L. ; Moses, Lina M. ; Jiang, Pan-Pan ; Lin, Aaron E. ; Schaffner, Stephen F. ; Bird, Brian ; Towner, Jonathan ; Mamoh, Mambu ; Gbakie, Michael ; Kanneh, Lansana ; Kargbo, David ; Massally, James L.B. ; Kamara, Fatima K. ; Konuwa, Edwin ; Sellu, Josephine ; Jalloh, Abdul A. ; Mustapha, Ibrahim ; Foday, Momoh ; Yillah, Mohamed ; Erickson, Bobbie R. ; Sealy, Tara ; Blau, Dianna ; Paddock, Christopher ; Brault, Aaron ; Amman, Brian ; Basile, Jane ; Bearden, Scott ; Belser, Jessica ; Bergeron, Eric ; Campbell, Shelley ; Chakrabarti, Ayan ; Dodd, Kimberly ; Flint, Mike ; Gibbons, Aridth ; Goodman, Christin ; Klena, John ; McMullan, Laura ; Morgan, Laura ; Russell, Brandy ; Salzer, Johanna ; Sanchez, Angela ; Wang, David ; Jungreis, Irwin ; Tomkins-Tinch, Christopher ; Kislyuk, Andrey ; Lin, Michael F. ; Chapman, Sinead ; MacInnis, Bronwyn ; Matthews, Ashley ; Bochicchio, James ; Hensley, Lisa E. ; Kuhn, Jens H. ; Nusbaum, Chad ; Schieffelin, John S. ; Birren, Bruce W. ; Forget, Marc ; Nichol, Stuart T. ; Palacios, Gustavo F. ; Ndiaye, Daouda ; Happi, Christian ; Gevao, Sahr M. ; Vandi, Mohamed A. ; Kargbo, Brima ; Holmes, Edward C. ; Bedford, Trevor ; Gnirke, Andreas ; Ströher, Ute ; Rambaut, Andrew ; Garry, Robert F. ; Sabeti, Pardis C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c488t-e9b0d31433f4cb5ebf248e65cd0d16871fa022f36f8324c1a80814aa3c3c750f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Biological Evolution</topic><topic>Disease Outbreaks</topic><topic>disease transmission</topic><topic>Ebolavirus</topic><topic>Ebolavirus - classification</topic><topic>Ebolavirus - genetics</topic><topic>Ebolavirus - isolation &amp; purification</topic><topic>evolution</topic><topic>genetic variation</topic><topic>genome</topic><topic>Genome, Viral</topic><topic>glycoproteins</topic><topic>Hemorrhagic Fever, Ebola - epidemiology</topic><topic>Hemorrhagic Fever, Ebola - transmission</topic><topic>Hemorrhagic Fever, Ebola - virology</topic><topic>Humans</topic><topic>Mutation</topic><topic>patients</topic><topic>sequence analysis</topic><topic>Sierra Leone</topic><topic>Sierra Leone - epidemiology</topic><topic>Specimen Handling</topic><topic>viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Daniel J.</creatorcontrib><creatorcontrib>Dudas, Gytis</creatorcontrib><creatorcontrib>Wohl, Shirlee</creatorcontrib><creatorcontrib>Goba, Augustine</creatorcontrib><creatorcontrib>Whitmer, Shannon L.M.</creatorcontrib><creatorcontrib>Andersen, Kristian G.</creatorcontrib><creatorcontrib>Sealfon, Rachel S.</creatorcontrib><creatorcontrib>Ladner, Jason T.</creatorcontrib><creatorcontrib>Kugelman, Jeffrey R.</creatorcontrib><creatorcontrib>Matranga, Christian B.</creatorcontrib><creatorcontrib>Winnicki, Sarah M.</creatorcontrib><creatorcontrib>Qu, James</creatorcontrib><creatorcontrib>Gire, Stephen K.</creatorcontrib><creatorcontrib>Gladden-Young, Adrianne</creatorcontrib><creatorcontrib>Jalloh, Simbirie</creatorcontrib><creatorcontrib>Nosamiefan, Dolo</creatorcontrib><creatorcontrib>Yozwiak, Nathan L.</creatorcontrib><creatorcontrib>Moses, Lina M.</creatorcontrib><creatorcontrib>Jiang, Pan-Pan</creatorcontrib><creatorcontrib>Lin, Aaron E.</creatorcontrib><creatorcontrib>Schaffner, Stephen F.</creatorcontrib><creatorcontrib>Bird, Brian</creatorcontrib><creatorcontrib>Towner, Jonathan</creatorcontrib><creatorcontrib>Mamoh, Mambu</creatorcontrib><creatorcontrib>Gbakie, Michael</creatorcontrib><creatorcontrib>Kanneh, Lansana</creatorcontrib><creatorcontrib>Kargbo, David</creatorcontrib><creatorcontrib>Massally, James L.B.</creatorcontrib><creatorcontrib>Kamara, Fatima K.</creatorcontrib><creatorcontrib>Konuwa, Edwin</creatorcontrib><creatorcontrib>Sellu, Josephine</creatorcontrib><creatorcontrib>Jalloh, Abdul A.</creatorcontrib><creatorcontrib>Mustapha, Ibrahim</creatorcontrib><creatorcontrib>Foday, Momoh</creatorcontrib><creatorcontrib>Yillah, Mohamed</creatorcontrib><creatorcontrib>Erickson, Bobbie R.</creatorcontrib><creatorcontrib>Sealy, Tara</creatorcontrib><creatorcontrib>Blau, Dianna</creatorcontrib><creatorcontrib>Paddock, Christopher</creatorcontrib><creatorcontrib>Brault, Aaron</creatorcontrib><creatorcontrib>Amman, Brian</creatorcontrib><creatorcontrib>Basile, Jane</creatorcontrib><creatorcontrib>Bearden, Scott</creatorcontrib><creatorcontrib>Belser, Jessica</creatorcontrib><creatorcontrib>Bergeron, Eric</creatorcontrib><creatorcontrib>Campbell, Shelley</creatorcontrib><creatorcontrib>Chakrabarti, Ayan</creatorcontrib><creatorcontrib>Dodd, Kimberly</creatorcontrib><creatorcontrib>Flint, Mike</creatorcontrib><creatorcontrib>Gibbons, Aridth</creatorcontrib><creatorcontrib>Goodman, Christin</creatorcontrib><creatorcontrib>Klena, John</creatorcontrib><creatorcontrib>McMullan, Laura</creatorcontrib><creatorcontrib>Morgan, Laura</creatorcontrib><creatorcontrib>Russell, Brandy</creatorcontrib><creatorcontrib>Salzer, Johanna</creatorcontrib><creatorcontrib>Sanchez, Angela</creatorcontrib><creatorcontrib>Wang, David</creatorcontrib><creatorcontrib>Jungreis, Irwin</creatorcontrib><creatorcontrib>Tomkins-Tinch, Christopher</creatorcontrib><creatorcontrib>Kislyuk, Andrey</creatorcontrib><creatorcontrib>Lin, Michael F.</creatorcontrib><creatorcontrib>Chapman, Sinead</creatorcontrib><creatorcontrib>MacInnis, Bronwyn</creatorcontrib><creatorcontrib>Matthews, Ashley</creatorcontrib><creatorcontrib>Bochicchio, James</creatorcontrib><creatorcontrib>Hensley, Lisa E.</creatorcontrib><creatorcontrib>Kuhn, Jens H.</creatorcontrib><creatorcontrib>Nusbaum, Chad</creatorcontrib><creatorcontrib>Schieffelin, John S.</creatorcontrib><creatorcontrib>Birren, Bruce W.</creatorcontrib><creatorcontrib>Forget, Marc</creatorcontrib><creatorcontrib>Nichol, Stuart T.</creatorcontrib><creatorcontrib>Palacios, Gustavo F.</creatorcontrib><creatorcontrib>Ndiaye, Daouda</creatorcontrib><creatorcontrib>Happi, Christian</creatorcontrib><creatorcontrib>Gevao, Sahr M.</creatorcontrib><creatorcontrib>Vandi, Mohamed A.</creatorcontrib><creatorcontrib>Kargbo, Brima</creatorcontrib><creatorcontrib>Holmes, Edward C.</creatorcontrib><creatorcontrib>Bedford, Trevor</creatorcontrib><creatorcontrib>Gnirke, Andreas</creatorcontrib><creatorcontrib>Ströher, Ute</creatorcontrib><creatorcontrib>Rambaut, Andrew</creatorcontrib><creatorcontrib>Garry, Robert F.</creatorcontrib><creatorcontrib>Sabeti, Pardis C.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Daniel J.</au><au>Dudas, Gytis</au><au>Wohl, Shirlee</au><au>Goba, Augustine</au><au>Whitmer, Shannon L.M.</au><au>Andersen, Kristian G.</au><au>Sealfon, Rachel S.</au><au>Ladner, Jason T.</au><au>Kugelman, Jeffrey R.</au><au>Matranga, Christian B.</au><au>Winnicki, Sarah M.</au><au>Qu, James</au><au>Gire, Stephen K.</au><au>Gladden-Young, Adrianne</au><au>Jalloh, Simbirie</au><au>Nosamiefan, Dolo</au><au>Yozwiak, Nathan L.</au><au>Moses, Lina M.</au><au>Jiang, Pan-Pan</au><au>Lin, Aaron E.</au><au>Schaffner, Stephen F.</au><au>Bird, Brian</au><au>Towner, Jonathan</au><au>Mamoh, Mambu</au><au>Gbakie, Michael</au><au>Kanneh, Lansana</au><au>Kargbo, David</au><au>Massally, James L.B.</au><au>Kamara, Fatima K.</au><au>Konuwa, Edwin</au><au>Sellu, Josephine</au><au>Jalloh, Abdul A.</au><au>Mustapha, Ibrahim</au><au>Foday, Momoh</au><au>Yillah, Mohamed</au><au>Erickson, Bobbie R.</au><au>Sealy, Tara</au><au>Blau, Dianna</au><au>Paddock, Christopher</au><au>Brault, Aaron</au><au>Amman, Brian</au><au>Basile, Jane</au><au>Bearden, Scott</au><au>Belser, Jessica</au><au>Bergeron, Eric</au><au>Campbell, Shelley</au><au>Chakrabarti, Ayan</au><au>Dodd, Kimberly</au><au>Flint, Mike</au><au>Gibbons, Aridth</au><au>Goodman, Christin</au><au>Klena, John</au><au>McMullan, Laura</au><au>Morgan, Laura</au><au>Russell, Brandy</au><au>Salzer, Johanna</au><au>Sanchez, Angela</au><au>Wang, David</au><au>Jungreis, Irwin</au><au>Tomkins-Tinch, Christopher</au><au>Kislyuk, Andrey</au><au>Lin, Michael F.</au><au>Chapman, Sinead</au><au>MacInnis, Bronwyn</au><au>Matthews, Ashley</au><au>Bochicchio, James</au><au>Hensley, Lisa E.</au><au>Kuhn, Jens H.</au><au>Nusbaum, Chad</au><au>Schieffelin, John S.</au><au>Birren, Bruce W.</au><au>Forget, Marc</au><au>Nichol, Stuart T.</au><au>Palacios, Gustavo F.</au><au>Ndiaye, Daouda</au><au>Happi, Christian</au><au>Gevao, Sahr M.</au><au>Vandi, Mohamed A.</au><au>Kargbo, Brima</au><au>Holmes, Edward C.</au><au>Bedford, Trevor</au><au>Gnirke, Andreas</au><au>Ströher, Ute</au><au>Rambaut, Andrew</au><au>Garry, Robert F.</au><au>Sabeti, Pardis C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>2015-06-18</date><risdate>2015</risdate><volume>161</volume><issue>7</issue><spage>1516</spage><epage>1526</epage><pages>1516-1526</pages><issn>0092-8674</issn><issn>1097-4172</issn><eissn>1097-4172</eissn><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. [Display omitted] •In Sierra Leone, transmission has primarily been within-country, not between-country•Infectious doses are large enough for intrahost variants to transmit between hosts•A prolonged epidemic removes deleterious mutations from the viral population•There is preliminary evidence for human RNA editing effects on the Ebola genome 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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26091036</pmid><doi>10.1016/j.cell.2015.06.007</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record>
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subjects Biological Evolution
Disease Outbreaks
disease transmission
Ebolavirus
Ebolavirus - classification
Ebolavirus - genetics
Ebolavirus - isolation & purification
evolution
genetic variation
genome
Genome, Viral
glycoproteins
Hemorrhagic Fever, Ebola - epidemiology
Hemorrhagic Fever, Ebola - transmission
Hemorrhagic Fever, Ebola - virology
Humans
Mutation
patients
sequence analysis
Sierra Leone
Sierra Leone - epidemiology
Specimen Handling
viruses
title Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone
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