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. 2016 Apr 29;2(4):e1600378.
doi: 10.1126/sciadv.1600378. eCollection 2016 Apr.

Reduced evolutionary rate in reemerged Ebola virus transmission chains

David J Blackley  1 , Michael R Wiley  2 , Jason T Ladner  2 , Mosoka Fallah  3 , Terrence Lo  1 , Merle L Gilbert  2 , Christopher Gregory  1 , Jonathan D'ambrozio  2 , Stewart Coulter  1 , Suzanne Mate  2 , Zephaniah Balogun  1 , Jeffrey Kugelman  2 , William Nwachukwu  1 , Karla Prieto  2 , Adolphus Yeiah  3 , Fred Amegashie  3 , Brian Kearney  2 , Meagan Wisniewski  2 , John Saindon  1 , Gary Schroth  4 , Lawrence Fakoli  5 , Joseph W Diclaro 2nd  6 , Jens H Kuhn  7 , Lisa E Hensley  7 , Peter B Jahrling  7 , Ute Ströher  1 , Stuart T Nichol  1 , Moses Massaquoi  3 , Francis Kateh  3 , Peter Clement  8 , Alex Gasasira  8 , Fatorma Bolay  5 , Stephan S Monroe  1 , Andrew Rambaut  9 , Mariano Sanchez-Lockhart  2 , A Scott Laney  1 , Tolbert Nyenswah  3 , Athalia Christie  1 , Gustavo Palacios  2
Affiliations

Reduced evolutionary rate in reemerged Ebola virus transmission chains

David J Blackley et al. Sci Adv. .

Abstract

On 29 June 2015, Liberia's respite from Ebola virus disease (EVD) was interrupted for the second time by a renewed outbreak ("flare-up") of seven confirmed cases. We demonstrate that, similar to the March 2015 flare-up associated with sexual transmission, this new flare-up was a reemergence of a Liberian transmission chain originating from a persistently infected source rather than a reintroduction from a reservoir or a neighboring country with active transmission. Although distinct, Ebola virus (EBOV) genomes from both flare-ups exhibit significantly low genetic divergence, indicating a reduced rate of EBOV evolution during persistent infection. Using this rate of change as a signature, we identified two additional EVD clusters that possibly arose from persistently infected sources. These findings highlight the risk of EVD flare-ups even after an outbreak is declared over.

Keywords: Ebola virus; Ebola virus disease; Liberia; Western Africa; flare-up; persistent infection; reduced evolutionary rate; reemerged; transmission chain.

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Figures

Fig. 1
Fig. 1. The Needowein flare-up represents the reemergence of an EBOV transmission chain from the Liberian portion of the Western African EVD outbreak.
(A) Median-joining haplotype network constructed from a full genome alignment of 583 Western African EBOV sequences (see table S3 for accession numbers). The dashed oval indicates the LB2 sublineage (SL2 lineage), which includes the sequences from the Needowein flare-up. Gray shading indicates the lineages that were circulating during February to October 2015 in Sierra Leone and Guinea (GN1, SL3, and SL4). (B) Median-joining haplotype network depicting the LB2 sublineage (see table S3 for accession numbers), including six sequenced genomes from the Barclay Farm cluster during August to September 2014 (purple). See table S1 for a description of the labeled substitutions (a to g).
Fig. 2
Fig. 2. Several EVD case clusters, including the Needowein flare-up (June to July 2015), are characterized by EBOV with lower-than-expected sequence divergence based on sampling date.
(A) Root-to-tip distance versus sampling date for the Liberian portion of the SL2 lineage, including sequences from Guinea and Mali linked to reintroductions from Liberia (5). Green, Needowein flare-up; pink, sexual transmission (1); blue, St. Paul Bridge cluster (8); orange, Guinean cluster; dashed lines, 95% prediction interval. (B) Temporal maximum clade credibility tree from BEAST (Bayesian evolutionary analysis by sampling trees). Circles represent sampled EBOV genomes colored as described in (A). For the Needowein flare-up (green) and the March 2015 case of sexual transmission (pink), the dashed lines represent the difference between the actual date of sampling (right) and the estimated sampling date from the BEAST analysis (left). The posterior distributions for the estimated sampling dates are shown below the tree.
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References

    1. Mate S. E., Kugelman J. R., Nyenswah T. G., Ladner J. T., Wiley M. R., Cordier-Lassalle T., Christie A., Schroth G. P., Gross S. M., Davies-Wayne G. J., Shinde S. A., Murugan R., Sieh S. B., Badio M., Fakoli L., Taweh F., de Wit E., van Doremalen N., Munster V. J., Pettitt J., Prieto K., Humrighouse B. W., Ströher U., DiClaro J. W., Hensley L. E., Schoepp R. J., Safronetz D., Fair J., Kuhn J. H., Blackley D. J., Laney A. S., Williams D. E., Lo T., Gasasira A., Nichol S. T., Formenty P., Kateh F. N., De Cock K. M., Bolay F., Sanchez-Lockhart M., Palacios G., Molecular evidence of sexual transmission of Ebola virus. N. Engl. J. Med. 373, 2448–2454 (2015). - PMC - PubMed
    1. Ladner J. T., Beitzel B., Chain P. S. G., Davenport M. G., Donaldson E. F., Frieman M., Kugelman J. R., Kuhn J. H., O’Rear J., Sabeti P. C., Wentworth D. E., Wiley M. R., Yu G.-Y.; Threat Characterization Consortium, Sozhamannan S., Bradburne C., Palacios G., Standards for sequencing viral genomes in the era of high-throughput sequencing. mBio 5, e01360-14 (2014). - PMC - PubMed
    1. Baize S., Pannetier D., Oestereich L., Rieger T., Koivogui L., Magassouba N., Soropogui B., Sow M. S., Keïta S., De Clerck H., Tiffany A., Dominguez G., Loua M., Traore A., Kolié M., Malano E. R., Heleze E., Bocquin A., Mely S., Raoul H., Caro V., Cadar D., Gabriel M., Pahlmann M., Tappe D., Schmidt-Chanasit J., Impouma B., Diallo A. K., Formenty P., Van Herp M., Günther S., Emergence of Zaire Ebola virus disease in Guinea. N. Engl. J. Med. 371, 1418–1425 (2014). - PubMed
    1. Gire S. K., Goba A., Andersen K. G., Sealfon R. S. G., Park D. J., Kanneh L., Jalloh S., Momoh M., Fullah M., Dudas G., Wohl S., Moses L. M., Yozwiak N. L., Winnicki S., Matranga C. B., Malboeuf C. M., Qu J., Gladden A. D., Schaffner S. F., Yang X., Jiang P. P., Nekoui M., Colubri A., Coomber M. R., Fonnie M., Moigboi A., Gbakie M., Kamara F. K., Tucker V., Konuwa E., Saffa S., Sellu J., Jalloh A. A., Kovoma A., Koninga J., Mustapha I., Kargbo K., Foday M., Yillah M., Kanneh F., Robert W., Massally J. L., Chapman S. B., Bochicchio J., Murphy C., Nusbaum C., Young S., Birren B. W., Grant D. S., Scheiffelin J. S., Lander E. S., Happi C., Gevao S. M., Gnirke A., Rambaut A., Garry R. F., Khan S. H., Sabeti P. C., Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science 345, 1369–1372 (2014). - PMC - PubMed
    1. Ladner J. T., Wiley M. R., Mate S., Dudas G., Prieto K., Lovett S., Nagle E. R., Beitzel B., Gilbert M. L., Fakoli L., Diclaro J. W. II, Schoepp R. J., Fair J., Kuhn J. H., Hensley L. E., Park D. J., Sabeti P. C., Rambaut A., Sanchez-Lockhart M., Bolay F. K., Kugelman J. R., Palacios G., Evolution and spread of Ebola virus in Liberia, 2014–2015. Cell Host Microbe 18, 659–669 (2015). - PMC - PubMed

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