Dose-Dependent Response to Infection with Ebola Virus in the Ferret Model and Evidence of Viral Evolution in the Eye

Robert J. Watson; Julia Tree; Susan A. Fotheringham; Yper Hall; Xiaofeng Dong; Kimberley Steeds; Jade Gouriet; Francisco J. Salguero; Christopher Burton; James Pitman; Linda Easterbrook; Kevin S. Richards; Jane Burton; Kevin Bewley; Christine Bruce; Julian A. Hiscox; Miles W. Carroll; Simon G.P. Funnell

doi:10.1128/JVI.00833-21

Dose-Dependent Response to Infection with Ebola Virus in the Ferret Model and Evidence of Viral Evolution in the Eye

Robert J. Watson^*, Julia Tree, Susan A. Fotheringham, Yper Hall, Xiaofeng Dong, Kimberley Steeds, Jade Gouriet, Francisco J. Salguero, Christopher Burton, James Pitman, Linda Easterbrook, Kevin S. Richards, Jane Burton, Kevin Bewley, Christine Bruce, Julian A. Hiscox, Miles W. Carroll, Simon G.P. Funnell

^*Corresponding author for this work

UK Health Security Agency

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

10 Citations (Scopus)

Abstract

Filoviruses cause high-consequence infections with limited approved medical countermeasures (MCMs). MCM development is dependent upon well-characterized animal models for the assessment of antiviral agents and vaccines. Following large-scale Ebola virus (EBOV) disease outbreaks in Africa, some survivors are left with long-term sequelae and persistent virus in immune-privileged sites for many years. We report the characterization of the ferret as a model for Ebola virus infection, reproducing disease and lethality observed in humans. The onset of clinical signs is rapid, and EBOV is detected in the blood, oral, and rectal swabs and all tissues studied. We identify viral RNA in the eye (a site of immune privilege) and report on specific genomic changes in EBOV present in this structure. Thus, the ferret model has utility in testing MCMs that prevent or treat long-term EBOV persistence in immune-privileged sites.

Original language	English
Article number	e00833-21
Journal	Journal of Virology
Volume	95
Issue number	24
DOIs	https://doi.org/10.1128/JVI.00833-21
Publication status	Published - Nov 2021

Bibliographical note

Funding Information:
We gratefully acknowledge the support from the Biological Investigations Group at the National Infection Service, PHE, Porton Down, United Kingdom. We also acknowledge and thank Andre Charlotte, NIS, PHE, UK, for assistance in the statistical design of the studies conducted.

Funding Information:
This work was funded by the Biomedical Advanced Research and Development Authority (BARDA) under contract HHS0100201700016I, order HHSO10033003T. The sequencing and informatics work was funded by a U.S. Food and Drug Administration Medical Countermeasures Initiative contract (HHSF223201710194C).

Publisher Copyright:
© 2021 American Society for Microbiology. All rights reserved.

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Watson, R. J., Tree, J., Fotheringham, S. A., Hall, Y., Dong, X., Steeds, K., Gouriet, J., Salguero, F. J., Burton, C., Pitman, J., Easterbrook, L., Richards, K. S., Burton, J., Bewley, K., Bruce, C., Hiscox, J. A., Carroll, M. W., & Funnell, S. G. P. (2021). Dose-Dependent Response to Infection with Ebola Virus in the Ferret Model and Evidence of Viral Evolution in the Eye. Journal of Virology, 95(24), Article e00833-21. https://doi.org/10.1128/JVI.00833-21

@article{56dfa178131340b889214595715ae949,

title = "Dose-Dependent Response to Infection with Ebola Virus in the Ferret Model and Evidence of Viral Evolution in the Eye",

abstract = "Filoviruses cause high-consequence infections with limited approved medical countermeasures (MCMs). MCM development is dependent upon well-characterized animal models for the assessment of antiviral agents and vaccines. Following large-scale Ebola virus (EBOV) disease outbreaks in Africa, some survivors are left with long-term sequelae and persistent virus in immune-privileged sites for many years. We report the characterization of the ferret as a model for Ebola virus infection, reproducing disease and lethality observed in humans. The onset of clinical signs is rapid, and EBOV is detected in the blood, oral, and rectal swabs and all tissues studied. We identify viral RNA in the eye (a site of immune privilege) and report on specific genomic changes in EBOV present in this structure. Thus, the ferret model has utility in testing MCMs that prevent or treat long-term EBOV persistence in immune-privileged sites.",

author = "Watson, {Robert J.} and Julia Tree and Fotheringham, {Susan A.} and Yper Hall and Xiaofeng Dong and Kimberley Steeds and Jade Gouriet and Salguero, {Francisco J.} and Christopher Burton and James Pitman and Linda Easterbrook and Richards, {Kevin S.} and Jane Burton and Kevin Bewley and Christine Bruce and Hiscox, {Julian A.} and Carroll, {Miles W.} and Funnell, {Simon G.P.}",

note = "Funding Information: We gratefully acknowledge the support from the Biological Investigations Group at the National Infection Service, PHE, Porton Down, United Kingdom. We also acknowledge and thank Andre Charlotte, NIS, PHE, UK, for assistance in the statistical design of the studies conducted. Funding Information: This work was funded by the Biomedical Advanced Research and Development Authority (BARDA) under contract HHS0100201700016I, order HHSO10033003T. The sequencing and informatics work was funded by a U.S. Food and Drug Administration Medical Countermeasures Initiative contract (HHSF223201710194C). Publisher Copyright: {\textcopyright} 2021 American Society for Microbiology. All rights reserved.",

year = "2021",

month = nov,

doi = "10.1128/JVI.00833-21",

language = "English",

volume = "95",

journal = "Journal of Virology",

issn = "0022-538X",

publisher = "American Society for Microbiology",

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Watson, RJ, Tree, J , Fotheringham, SA, Hall, Y, Dong, X, Steeds, K, Gouriet, J, Salguero, FJ, Burton, C, Pitman, J , Easterbrook, L , Richards, KS , Burton, J , Bewley, K, Bruce, C, Hiscox, JA, Carroll, MW & Funnell, SGP 2021, 'Dose-Dependent Response to Infection with Ebola Virus in the Ferret Model and Evidence of Viral Evolution in the Eye', Journal of Virology, vol. 95, no. 24, e00833-21. https://doi.org/10.1128/JVI.00833-21

TY - JOUR

T1 - Dose-Dependent Response to Infection with Ebola Virus in the Ferret Model and Evidence of Viral Evolution in the Eye

AU - Watson, Robert J.

AU - Tree, Julia

AU - Fotheringham, Susan A.

AU - Hall, Yper

AU - Dong, Xiaofeng

AU - Steeds, Kimberley

AU - Gouriet, Jade

AU - Salguero, Francisco J.

AU - Burton, Christopher

AU - Pitman, James

AU - Easterbrook, Linda

AU - Richards, Kevin S.

AU - Burton, Jane

AU - Bewley, Kevin

AU - Bruce, Christine

AU - Hiscox, Julian A.

AU - Carroll, Miles W.

AU - Funnell, Simon G.P.

N1 - Funding Information: We gratefully acknowledge the support from the Biological Investigations Group at the National Infection Service, PHE, Porton Down, United Kingdom. We also acknowledge and thank Andre Charlotte, NIS, PHE, UK, for assistance in the statistical design of the studies conducted. Funding Information: This work was funded by the Biomedical Advanced Research and Development Authority (BARDA) under contract HHS0100201700016I, order HHSO10033003T. The sequencing and informatics work was funded by a U.S. Food and Drug Administration Medical Countermeasures Initiative contract (HHSF223201710194C). Publisher Copyright: © 2021 American Society for Microbiology. All rights reserved.

PY - 2021/11

Y1 - 2021/11

N2 - Filoviruses cause high-consequence infections with limited approved medical countermeasures (MCMs). MCM development is dependent upon well-characterized animal models for the assessment of antiviral agents and vaccines. Following large-scale Ebola virus (EBOV) disease outbreaks in Africa, some survivors are left with long-term sequelae and persistent virus in immune-privileged sites for many years. We report the characterization of the ferret as a model for Ebola virus infection, reproducing disease and lethality observed in humans. The onset of clinical signs is rapid, and EBOV is detected in the blood, oral, and rectal swabs and all tissues studied. We identify viral RNA in the eye (a site of immune privilege) and report on specific genomic changes in EBOV present in this structure. Thus, the ferret model has utility in testing MCMs that prevent or treat long-term EBOV persistence in immune-privileged sites.

AB - Filoviruses cause high-consequence infections with limited approved medical countermeasures (MCMs). MCM development is dependent upon well-characterized animal models for the assessment of antiviral agents and vaccines. Following large-scale Ebola virus (EBOV) disease outbreaks in Africa, some survivors are left with long-term sequelae and persistent virus in immune-privileged sites for many years. We report the characterization of the ferret as a model for Ebola virus infection, reproducing disease and lethality observed in humans. The onset of clinical signs is rapid, and EBOV is detected in the blood, oral, and rectal swabs and all tissues studied. We identify viral RNA in the eye (a site of immune privilege) and report on specific genomic changes in EBOV present in this structure. Thus, the ferret model has utility in testing MCMs that prevent or treat long-term EBOV persistence in immune-privileged sites.

UR - http://www.scopus.com/inward/record.url?scp=85120054393&partnerID=8YFLogxK

U2 - 10.1128/JVI.00833-21

DO - 10.1128/JVI.00833-21

M3 - Article

C2 - 34586862

AN - SCOPUS:85120054393

SN - 0022-538X

VL - 95

JO - Journal of Virology

JF - Journal of Virology

IS - 24

M1 - e00833-21

ER -

Dose-Dependent Response to Infection with Ebola Virus in the Ferret Model and Evidence of Viral Evolution in the Eye

Abstract

Bibliographical note

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