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

Park DJ1, Dudas G2, Wohl S3, Goba A4, Whitmer SL5, Andersen KG6, Sealfon RS7, Ladner JT8, Kugelman JR8, Matranga CB9, Winnicki SM3, Qu J9, Gire SK3,Gladden-Young A9, Jalloh S4, Nosamiefan D9, Yozwiak NL3, Moses LM10, Jiang PP3, Lin AE3, Schaffner SF3, Bird B5, Towner J5, Mamoh M4, Gbakie M4,Kanneh L4, Kargbo D4, Massally JL4, Kamara FK4, Konuwa E4, Sellu J4, Jalloh AA4, Mustapha I4, Foday M4, Yillah M4, Erickson BR5, Sealy T5, Blau D5,Paddock C5, Brault A5, Amman B5, Basile J5, Bearden S5, Belser J5, Bergeron E5, Campbell S5, Chakrabarti A5, Dodd K5, Flint M5, Gibbons A5, Goodman C5,Klena J5, McMullan L5, Morgan L5, Russell B5, Salzer J5, Sanchez A5, Wang D5, Jungreis I11, Tomkins-Tinch C9, Kislyuk A12, Lin MF12, Chapman S9, MacInnis B9, Matthews A3, Bochicchio J9, Hensley LE13, Kuhn JH13, Nusbaum C9, Schieffelin JS10, Birren BW9, Forget M14, Nichol ST5, Palacios GF8, Ndiaye D15,Happi C16, Gevao SM17, Vandi MA18, Kargbo B18, Holmes EC19, Bedford T20, Gnirke A9, Ströher U5, Rambaut A21, Garry RF10, Sabeti PC22.

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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.