Interferon- therapy prolongs survival in rhesus macaque models of ebola and marburg hemorrhagic fever

Lauren M. Smith; Lisa E. Hensley; Thomas W. Geisbert; Joshua Johnson; Andrea Stossel; Anna Honko; Judy Y. Yen; Joan Geisbert; Jason Paragas; Elizabeth Fritz; Gene Olinger; Howard A. Young; Kathleen H. Rubins; Christopher L. Karp

doi:10.1093/infdis/jis921

Interferon- therapy prolongs survival in rhesus macaque models of ebola and marburg hemorrhagic fever

Lauren M. Smith, Lisa E. Hensley, Thomas W. Geisbert, Joshua Johnson, Andrea Stossel, Anna Honko, Judy Y. Yen, Joan Geisbert, Jason Paragas, Elizabeth Fritz, Gene Olinger, Howard A. Young, Kathleen H. Rubins, Christopher L. Karp

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

98 Scopus citations

Abstract

There is a clear need for novel, effective therapeutic approaches to hemorrhagic fever due to filoviruses. Ebola virus hemorrhagic fever is associated with robust interferon (IFN)- production, with plasma concentrations of IFN- that greatly (60- to 100-fold) exceed those seen in other viral infections, but little IFN- production. While all of the type I IFNs signal through the same receptor complex, both quantitative and qualitative differences in biological activity are observed after stimulation of the receptor complex with different type I IFNs. Taken together, this suggested potential for IFN-therapy in filovirus infection. Here we show that early postexposure treatment with IFN-significantly increased survival time of rhesus macaques infected with a lethal dose of Ebola virus, although it failed to alter mortality. Early treatment with IFN- also significantly increased survival time after Marburg virus infection. IFN- may have promise as an adjunctive postexposure therapy in filovirus infection.

Original language	English (US)
Pages (from-to)	310-318
Number of pages	9
Journal	Journal of Infectious Diseases
Volume	208
Issue number	2
DOIs	https://doi.org/10.1093/infdis/jis921
State	Published - Jul 15 2013
Externally published	Yes

Keywords

Filovirus
IFN-Ebola virus
Marburg virus
type I interferon

ASJC Scopus subject areas

General Medicine

Access to Document

10.1093/infdis/jis921

Cite this

Smith, L. M., Hensley, L. E., Geisbert, T. W., Johnson, J., Stossel, A., Honko, A., Yen, J. Y., Geisbert, J., Paragas, J., Fritz, E., Olinger, G., Young, H. A., Rubins, K. H., & Karp, C. L. (2013). Interferon- therapy prolongs survival in rhesus macaque models of ebola and marburg hemorrhagic fever. Journal of Infectious Diseases, 208(2), 310-318. https://doi.org/10.1093/infdis/jis921

Smith, LM, Hensley, LE, Geisbert, TW, Johnson, J, Stossel, A, Honko, A, Yen, JY, Geisbert, J, Paragas, J, Fritz, E, Olinger, G, Young, HA, Rubins, KH & Karp, CL 2013, 'Interferon- therapy prolongs survival in rhesus macaque models of ebola and marburg hemorrhagic fever', Journal of Infectious Diseases, vol. 208, no. 2, pp. 310-318. https://doi.org/10.1093/infdis/jis921

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title = "Interferon- therapy prolongs survival in rhesus macaque models of ebola and marburg hemorrhagic fever",

abstract = "There is a clear need for novel, effective therapeutic approaches to hemorrhagic fever due to filoviruses. Ebola virus hemorrhagic fever is associated with robust interferon (IFN)- production, with plasma concentrations of IFN- that greatly (60- to 100-fold) exceed those seen in other viral infections, but little IFN- production. While all of the type I IFNs signal through the same receptor complex, both quantitative and qualitative differences in biological activity are observed after stimulation of the receptor complex with different type I IFNs. Taken together, this suggested potential for IFN-therapy in filovirus infection. Here we show that early postexposure treatment with IFN-significantly increased survival time of rhesus macaques infected with a lethal dose of Ebola virus, although it failed to alter mortality. Early treatment with IFN- also significantly increased survival time after Marburg virus infection. IFN- may have promise as an adjunctive postexposure therapy in filovirus infection.",

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author = "Smith, {Lauren M.} and Hensley, {Lisa E.} and Geisbert, {Thomas W.} and Joshua Johnson and Andrea Stossel and Anna Honko and Yen, {Judy Y.} and Joan Geisbert and Jason Paragas and Elizabeth Fritz and Gene Olinger and Young, {Howard A.} and Rubins, {Kathleen H.} and Karp, {Christopher L.}",

note = "Funding Information: Financial support. This work was funded by JSTO-CBD/DTRA (Projects 19595 4.10009_06_RD_B and 19585 4.10037_07_RD_B to L. E. H.), National Institute of Allergy and Infectious Diseases (grants AI053539 to C. L. K. and AI057159 to L. E. H.), and Cincinnati Children{\textquoteright}s Hospital Medical Center (Translational Research Initiative Grant to C. L. K). L. M. S. was supported by an appointment to the Student Research Participation Program at the US Army Medical Research and Material Command administered by the Oak Ridge Institute for Science and Education, a Stanford URP Major Grant, and National Science Foundation Graduate Research Fellowship DGE-1147470. Potential conflicts of interest. All authors: No reported conflicts.",

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N2 - There is a clear need for novel, effective therapeutic approaches to hemorrhagic fever due to filoviruses. Ebola virus hemorrhagic fever is associated with robust interferon (IFN)- production, with plasma concentrations of IFN- that greatly (60- to 100-fold) exceed those seen in other viral infections, but little IFN- production. While all of the type I IFNs signal through the same receptor complex, both quantitative and qualitative differences in biological activity are observed after stimulation of the receptor complex with different type I IFNs. Taken together, this suggested potential for IFN-therapy in filovirus infection. Here we show that early postexposure treatment with IFN-significantly increased survival time of rhesus macaques infected with a lethal dose of Ebola virus, although it failed to alter mortality. Early treatment with IFN- also significantly increased survival time after Marburg virus infection. IFN- may have promise as an adjunctive postexposure therapy in filovirus infection.

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Interferon- therapy prolongs survival in rhesus macaque models of ebola and marburg hemorrhagic fever

Abstract

Keywords

ASJC Scopus subject areas

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