Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone.
Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone.
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DOI：
10.1016/j.cell.2015.06.007
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发表时间：
2015-06-18
期刊：
影响因子：
64.5
通讯作者：
Sabeti PC
中科院分区：
文献类型：
--
作者：
Park DJ;Dudas G;Wohl S;Goba A;Whitmer SL;Andersen KG;Sealfon RS;Ladner JT;Kugelman JR;Matranga CB;Winnicki SM;Qu J;Gire SK;Gladden-Young A;Jalloh S;Nosamiefan D;Yozwiak NL;Moses LM;Jiang PP;Lin AE;Schaffner SF;Bird B;Towner J;Mamoh M;Gbakie M;Kanneh L;Kargbo D;Massally JL;Kamara FK;Konuwa E;Sellu J;Jalloh AA;Mustapha I;Foday M;Yillah M;Erickson BR;Sealy T;Blau D;Paddock C;Brault A;Amman B;Basile J;Bearden S;Belser J;Bergeron E;Campbell S;Chakrabarti A;Dodd K;Flint M;Gibbons A;Goodman C;Klena J;McMullan L;Morgan L;Russell B;Salzer J;Sanchez A;Wang D;Jungreis I;Tomkins-Tinch C;Kislyuk A;Lin MF;Chapman S;MacInnis B;Matthews A;Bochicchio J;Hensley LE;Kuhn JH;Nusbaum C;Schieffelin JS;Birren BW;Forget M;Nichol ST;Palacios GF;Ndiaye D;Happi C;Gevao SM;Vandi MA;Kargbo B;Holmes EC;Bedford T;Gnirke A;Ströher U;Rambaut A;Garry RF;Sabeti PC
2013-2015年埃博拉病毒病（EVD）流行是由埃博拉病毒的Makona变体（EBOV）引起的。在疫情早期，基因组测序为了解病毒进化和传播提供了线索，并为疫情应对提供了重要信息。在这里，我们分析了塞拉利昂7个月内采样的232名患者的序列，沿着86个先前发布的流行病早期基因组。我们确认在塞拉利昂境内持续存在人与人之间的传播，没有发现埃博拉病毒在首次引入后跨越国界进口或出口的证据。使用高深度重复测序，我们观察到宿主间传播和宿主内遗传变异的反复出现。我们追踪纯化选择在抑制非同义突变随时间积累方面的影响。最后，我们注意到EBOV糖蛋白的粘蛋白样结构域的变化，值得进一步研究。这些发现阐明了EBOV在该地区的运动，并描述了病毒在长期人际传播过程中的演变。在塞拉利昂，传播主要是在国内，而不是在国家之间感染剂量足够大，宿主内变异可以在宿主之间传播长期的流行病消除了病毒种群中的有害突变有初步证据表明人类RNA编辑对埃博拉病毒基因组的影响对塞拉利昂7个月内采样的232名患者的埃博拉病毒基因组进行了测序。宿主内遗传变异的传播表明在传播过程中有足够高的感染剂量。人类宿主可能导致埃博拉病毒基因组的直接改变。
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. 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.