Elucidating variations in the nucleotide sequence of Ebola virus associated with increasing pathogenicity

Stuart D. Dowall; David A. Matthews; Isabel Garcia-Dorival; Irene Taylor; John Kenny; Christiane Hertz-Fowler; Neil Hall; Kara Corbin-Lickfett; Cyril Empig; Kyle Schlunegger; John N. Barr; Miles W. Carroll; Roger Hewson; Julian A. Hiscox

doi:10.1186/s13059-014-0540-x

Elucidating variations in the nucleotide sequence of Ebola virus associated with increasing pathogenicity

Stuart D. Dowall, David A. Matthews, Isabel Garcia-Dorival, Irene Taylor, John Kenny, Christiane Hertz-Fowler, Neil Hall, Kara Corbin-Lickfett, Cyril Empig, Kyle Schlunegger, John N. Barr, Miles W. Carroll, Roger Hewson, Julian A. Hiscox

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

42 Citations (Scopus)

Abstract

BACKGROUND: Ebolaviruses causes a severe and often fatal hemorrhagic fever in humans, with some species such as Ebola virus having case fatality rates approaching 90%. Currently the worst Ebola virus outbreak since the disease was discovered is occurring in West Africa. Although thought to be a zoonotic infection, a concern is that with increasing numbers of humans being infected, Ebola virus variants could be selected which are better adapted for human-to-human transmission.

RESULTS: To investigate whether genetic changes in Ebola virus become established in response to adaptation in a different host, a guinea pig model of infection was used. In this experimental system, guinea pigs were infected with Ebola virus (EBOV), which initially did not cause disease. To simulate transmission to uninfected individuals, the virus was serially passaged five times in naive animals. As the virus was passaged, virulence increased and clinical effects were observed in the guinea pig. An RNAseq and consensus mapping approach was then used to evaluate potential nucleotide changes in the Ebola virus genome at each passage.

CONCLUSIONS: Upon passage in the guinea pig model, EBOV become more virulent, RNA editing and also coding changes in key proteins become established. The data suggest that the initial evolutionary trajectory of EBOV in a new host can lead to a gain in virulence. Given the circumstances of the sustained transmission of EBOV in the current outbreak in West Africa, increases in virulence may be associated with prolonged and uncontrolled epidemics of EBOV.

Original language	English
Article number	540
Pages (from-to)	540
Number of pages	1
Journal	Genome Biology
Volume	15
Issue number	11
DOIs	https://doi.org/10.1186/s13059-014-0540-x
Publication status	Published - 2014

Bibliographical note

Funding Information:
The in vivo work was supported by a Transformational Medical Technologies program contract HDTRA1-08-C-003 from the Department of Defense Chemical and Biological Defense program through the Defense Threat Reduction Agency (DTRA) (USA). We would like to thank Charlotte Nelson and Anita Lucaci at the University of Liverpool Centre for Genome Research for library preparation and sequence generation. The views expressed in this publication are those of the authors and not necessarily those of the funding or participant organisations.

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Dowall, S. D., Matthews, D. A., Garcia-Dorival, I., Taylor, I., Kenny, J., Hertz-Fowler, C., Hall, N., Corbin-Lickfett, K., Empig, C., Schlunegger, K., Barr, J. N., Carroll, M. W., Hewson, R., & Hiscox, J. A. (2014). Elucidating variations in the nucleotide sequence of Ebola virus associated with increasing pathogenicity. Genome Biology, 15(11), 540. Article 540. https://doi.org/10.1186/s13059-014-0540-x

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title = "Elucidating variations in the nucleotide sequence of Ebola virus associated with increasing pathogenicity",

abstract = "BACKGROUND: Ebolaviruses causes a severe and often fatal hemorrhagic fever in humans, with some species such as Ebola virus having case fatality rates approaching 90%. Currently the worst Ebola virus outbreak since the disease was discovered is occurring in West Africa. Although thought to be a zoonotic infection, a concern is that with increasing numbers of humans being infected, Ebola virus variants could be selected which are better adapted for human-to-human transmission.RESULTS: To investigate whether genetic changes in Ebola virus become established in response to adaptation in a different host, a guinea pig model of infection was used. In this experimental system, guinea pigs were infected with Ebola virus (EBOV), which initially did not cause disease. To simulate transmission to uninfected individuals, the virus was serially passaged five times in naive animals. As the virus was passaged, virulence increased and clinical effects were observed in the guinea pig. An RNAseq and consensus mapping approach was then used to evaluate potential nucleotide changes in the Ebola virus genome at each passage.CONCLUSIONS: Upon passage in the guinea pig model, EBOV become more virulent, RNA editing and also coding changes in key proteins become established. The data suggest that the initial evolutionary trajectory of EBOV in a new host can lead to a gain in virulence. Given the circumstances of the sustained transmission of EBOV in the current outbreak in West Africa, increases in virulence may be associated with prolonged and uncontrolled epidemics of EBOV.",

author = "Dowall, {Stuart D.} and Matthews, {David A.} and Isabel Garcia-Dorival and Irene Taylor and John Kenny and Christiane Hertz-Fowler and Neil Hall and Kara Corbin-Lickfett and Cyril Empig and Kyle Schlunegger and Barr, {John N.} and Carroll, {Miles W.} and Roger Hewson and Hiscox, {Julian A.}",

note = "Funding Information: The in vivo work was supported by a Transformational Medical Technologies program contract HDTRA1-08-C-003 from the Department of Defense Chemical and Biological Defense program through the Defense Threat Reduction Agency (DTRA) (USA). We would like to thank Charlotte Nelson and Anita Lucaci at the University of Liverpool Centre for Genome Research for library preparation and sequence generation. The views expressed in this publication are those of the authors and not necessarily those of the funding or participant organisations.",

year = "2014",

doi = "10.1186/s13059-014-0540-x",

language = "English",

volume = "15",

pages = "540",

journal = "Genome Biology",

issn = "1474-7596",

publisher = "BioMed Central Ltd.",

number = "11",

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Dowall, SD, Matthews, DA, Garcia-Dorival, I, Taylor, I, Kenny, J, Hertz-Fowler, C, Hall, N, Corbin-Lickfett, K, Empig, C, Schlunegger, K, Barr, JN, Carroll, MW, Hewson, R & Hiscox, JA 2014, 'Elucidating variations in the nucleotide sequence of Ebola virus associated with increasing pathogenicity', Genome Biology, vol. 15, no. 11, 540, pp. 540. https://doi.org/10.1186/s13059-014-0540-x

TY - JOUR

T1 - Elucidating variations in the nucleotide sequence of Ebola virus associated with increasing pathogenicity

AU - Dowall, Stuart D.

AU - Matthews, David A.

AU - Garcia-Dorival, Isabel

AU - Taylor, Irene

AU - Kenny, John

AU - Hertz-Fowler, Christiane

AU - Hall, Neil

AU - Corbin-Lickfett, Kara

AU - Empig, Cyril

AU - Schlunegger, Kyle

AU - Barr, John N.

AU - Carroll, Miles W.

AU - Hewson, Roger

AU - Hiscox, Julian A.

N1 - Funding Information: The in vivo work was supported by a Transformational Medical Technologies program contract HDTRA1-08-C-003 from the Department of Defense Chemical and Biological Defense program through the Defense Threat Reduction Agency (DTRA) (USA). We would like to thank Charlotte Nelson and Anita Lucaci at the University of Liverpool Centre for Genome Research for library preparation and sequence generation. The views expressed in this publication are those of the authors and not necessarily those of the funding or participant organisations.

PY - 2014

Y1 - 2014

N2 - BACKGROUND: Ebolaviruses causes a severe and often fatal hemorrhagic fever in humans, with some species such as Ebola virus having case fatality rates approaching 90%. Currently the worst Ebola virus outbreak since the disease was discovered is occurring in West Africa. Although thought to be a zoonotic infection, a concern is that with increasing numbers of humans being infected, Ebola virus variants could be selected which are better adapted for human-to-human transmission.RESULTS: To investigate whether genetic changes in Ebola virus become established in response to adaptation in a different host, a guinea pig model of infection was used. In this experimental system, guinea pigs were infected with Ebola virus (EBOV), which initially did not cause disease. To simulate transmission to uninfected individuals, the virus was serially passaged five times in naive animals. As the virus was passaged, virulence increased and clinical effects were observed in the guinea pig. An RNAseq and consensus mapping approach was then used to evaluate potential nucleotide changes in the Ebola virus genome at each passage.CONCLUSIONS: Upon passage in the guinea pig model, EBOV become more virulent, RNA editing and also coding changes in key proteins become established. The data suggest that the initial evolutionary trajectory of EBOV in a new host can lead to a gain in virulence. Given the circumstances of the sustained transmission of EBOV in the current outbreak in West Africa, increases in virulence may be associated with prolonged and uncontrolled epidemics of EBOV.

AB - BACKGROUND: Ebolaviruses causes a severe and often fatal hemorrhagic fever in humans, with some species such as Ebola virus having case fatality rates approaching 90%. Currently the worst Ebola virus outbreak since the disease was discovered is occurring in West Africa. Although thought to be a zoonotic infection, a concern is that with increasing numbers of humans being infected, Ebola virus variants could be selected which are better adapted for human-to-human transmission.RESULTS: To investigate whether genetic changes in Ebola virus become established in response to adaptation in a different host, a guinea pig model of infection was used. In this experimental system, guinea pigs were infected with Ebola virus (EBOV), which initially did not cause disease. To simulate transmission to uninfected individuals, the virus was serially passaged five times in naive animals. As the virus was passaged, virulence increased and clinical effects were observed in the guinea pig. An RNAseq and consensus mapping approach was then used to evaluate potential nucleotide changes in the Ebola virus genome at each passage.CONCLUSIONS: Upon passage in the guinea pig model, EBOV become more virulent, RNA editing and also coding changes in key proteins become established. The data suggest that the initial evolutionary trajectory of EBOV in a new host can lead to a gain in virulence. Given the circumstances of the sustained transmission of EBOV in the current outbreak in West Africa, increases in virulence may be associated with prolonged and uncontrolled epidemics of EBOV.

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DO - 10.1186/s13059-014-0540-x

M3 - Article

C2 - 25416632

AN - SCOPUS:84965191521

SN - 1474-7596

VL - 15

SP - 540

JO - Genome Biology

JF - Genome Biology

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ER -

Elucidating variations in the nucleotide sequence of Ebola virus associated with increasing pathogenicity

Abstract

Bibliographical note

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