Active Ebola Virus Replication and Heterogeneous Evolutionary Rates in EVD Survivors

Ebola Virus Persistence Study Group; Shannon L M Whitmer; Jason T. Ladner; Michael R. Wiley; Ketan J Patel; Gytis Dudas; Andrew Rambaut; Foday Sahr; Karla Prieto; Samuel S. Shepard; Ellie Carmody; Barbara Knust; Dhamari Naidoo; Gibrilla Deen; Pierre Formenty; Stuart T. Nichol; Gustavo F. Palacios; Ute Ströher

doi:10.1016/j.celrep.2018.01.008

Active Ebola Virus Replication and Heterogeneous Evolutionary Rates in EVD Survivors

Ebola Virus Persistence Study Group, Shannon L M Whitmer, Jason T. Ladner, Michael R. Wiley, Ketan J Patel, Gytis Dudas, Andrew Rambaut, Foday Sahr, Karla Prieto, Samuel S. Shepard, Ellie Carmody, Barbara Knust, Dhamari Naidoo, Gibrilla Deen, Pierre Formenty, Stuart T. Nichol, Gustavo F. Palacios, Ute Ströher

School of Biological Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

Following cessation of continuous Ebola virus (EBOV) transmission within Western Africa, sporadic EBOV disease (EVD) cases continued to re-emerge beyond the viral incubation period. Epidemiological and genomic evidence strongly suggests that this represented transmission from EVD survivors. To investigate whether persistent infections are characterized by ongoing viral replication, we sequenced EBOV from the semen of nine EVD survivors and a subset of corresponding acute specimens. EBOV evolutionary rates during persistence were either similar to or reduced relative to acute infection rates. Active EBOV replication/transcription continued during convalescence, but decreased over time, consistent with viral persistence rather than viral latency. Patterns of genetic divergence suggest a moderate relaxation of selective constraints within the sGP carboxy-terminal tail during persistent infections, but do not support widespread diversifying selection. Altogether, our data illustrate that EBOV persistence in semen, urine, and aqueous humor is not a quiescent or latent infection.

Original language	English
Pages (from-to)	1159-1168
Number of pages	10
Journal	Cell Reports
Volume	22
Issue number	5
DOIs	https://doi.org/10.1016/j.celrep.2018.01.008
Publication status	Published - 30 Jan 2018

Keywords

EVD survivors
Ebola virus
RNA hyper-editing
evolutionary pressure
evolutionary rates
persistent viral infection

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10.1016/j.celrep.2018.01.008

Active Ebola Virus PUB OA CC BY NC ND PIIS2211124718300081
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Ebola Virus Persistence Study Group, Whitmer, S. L. M., Ladner, JT., Wiley, M. R., Patel, K. J., Dudas, G., Rambaut, A., Sahr, F., Prieto, K., Shepard, S. S., Carmody, E., Knust, B., Naidoo, D., Deen, G., Formenty, P., Nichol, ST., Palacios, GF., & Ströher, U. (2018). Active Ebola Virus Replication and Heterogeneous Evolutionary Rates in EVD Survivors. Cell Reports, 22(5), 1159-1168. https://doi.org/10.1016/j.celrep.2018.01.008

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title = "Active Ebola Virus Replication and Heterogeneous Evolutionary Rates in EVD Survivors",

abstract = "Following cessation of continuous Ebola virus (EBOV) transmission within Western Africa, sporadic EBOV disease (EVD) cases continued to re-emerge beyond the viral incubation period. Epidemiological and genomic evidence strongly suggests that this represented transmission from EVD survivors. To investigate whether persistent infections are characterized by ongoing viral replication, we sequenced EBOV from the semen of nine EVD survivors and a subset of corresponding acute specimens. EBOV evolutionary rates during persistence were either similar to or reduced relative to acute infection rates. Active EBOV replication/transcription continued during convalescence, but decreased over time, consistent with viral persistence rather than viral latency. Patterns of genetic divergence suggest a moderate relaxation of selective constraints within the sGP carboxy-terminal tail during persistent infections, but do not support widespread diversifying selection. Altogether, our data illustrate that EBOV persistence in semen, urine, and aqueous humor is not a quiescent or latent infection.",

keywords = "EVD survivors, Ebola virus, RNA hyper-editing, evolutionary pressure, evolutionary rates, persistent viral infection",

author = "{Ebola Virus Persistence Study Group} and Whitmer, {Shannon L M} and Jason T. Ladner and Wiley, {Michael R.} and Patel, {Ketan J} and Gytis Dudas and Andrew Rambaut and Foday Sahr and Karla Prieto and Shepard, {Samuel S.} and Ellie Carmody and Barbara Knust and Dhamari Naidoo and Gibrilla Deen and Pierre Formenty and Stuart T. Nichol and Gustavo F. Palacios and Ute Str{\"o}her",

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Ebola Virus Persistence Study Group, Whitmer, SLM, Ladner, JT, Wiley, MR, Patel, KJ, Dudas, G, Rambaut, A, Sahr, F, Prieto, K, Shepard, SS, Carmody, E, Knust, B, Naidoo, D, Deen, G, Formenty, P, Nichol, ST, Palacios, GF & Ströher, U 2018, 'Active Ebola Virus Replication and Heterogeneous Evolutionary Rates in EVD Survivors', Cell Reports, vol. 22, no. 5, pp. 1159-1168. https://doi.org/10.1016/j.celrep.2018.01.008

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T1 - Active Ebola Virus Replication and Heterogeneous Evolutionary Rates in EVD Survivors

AU - Ebola Virus Persistence Study Group

AU - Whitmer, Shannon L M

AU - Ladner, Jason T.

AU - Wiley, Michael R.

AU - Patel, Ketan J

AU - Dudas, Gytis

AU - Rambaut, Andrew

AU - Sahr, Foday

AU - Prieto, Karla

AU - Shepard, Samuel S.

AU - Carmody, Ellie

AU - Knust, Barbara

AU - Naidoo, Dhamari

AU - Deen, Gibrilla

AU - Formenty, Pierre

AU - Nichol, Stuart T.

AU - Palacios, Gustavo F.

AU - Ströher, Ute

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N2 - Following cessation of continuous Ebola virus (EBOV) transmission within Western Africa, sporadic EBOV disease (EVD) cases continued to re-emerge beyond the viral incubation period. Epidemiological and genomic evidence strongly suggests that this represented transmission from EVD survivors. To investigate whether persistent infections are characterized by ongoing viral replication, we sequenced EBOV from the semen of nine EVD survivors and a subset of corresponding acute specimens. EBOV evolutionary rates during persistence were either similar to or reduced relative to acute infection rates. Active EBOV replication/transcription continued during convalescence, but decreased over time, consistent with viral persistence rather than viral latency. Patterns of genetic divergence suggest a moderate relaxation of selective constraints within the sGP carboxy-terminal tail during persistent infections, but do not support widespread diversifying selection. Altogether, our data illustrate that EBOV persistence in semen, urine, and aqueous humor is not a quiescent or latent infection.

AB - Following cessation of continuous Ebola virus (EBOV) transmission within Western Africa, sporadic EBOV disease (EVD) cases continued to re-emerge beyond the viral incubation period. Epidemiological and genomic evidence strongly suggests that this represented transmission from EVD survivors. To investigate whether persistent infections are characterized by ongoing viral replication, we sequenced EBOV from the semen of nine EVD survivors and a subset of corresponding acute specimens. EBOV evolutionary rates during persistence were either similar to or reduced relative to acute infection rates. Active EBOV replication/transcription continued during convalescence, but decreased over time, consistent with viral persistence rather than viral latency. Patterns of genetic divergence suggest a moderate relaxation of selective constraints within the sGP carboxy-terminal tail during persistent infections, but do not support widespread diversifying selection. Altogether, our data illustrate that EBOV persistence in semen, urine, and aqueous humor is not a quiescent or latent infection.

KW - EVD survivors

KW - Ebola virus

KW - RNA hyper-editing

KW - evolutionary pressure

KW - evolutionary rates

KW - persistent viral infection

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DO - 10.1016/j.celrep.2018.01.008

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VL - 22

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EP - 1168

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 5

ER -

Active Ebola Virus Replication and Heterogeneous Evolutionary Rates in EVD Survivors

Abstract

Keywords

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