Interferon-β Therapy Prolongs Survival in Rhesus Macaque Models of Ebola and Marburg Hemorrhagic Fever

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2012 Dec 21

PMID 23255566

Citations 59

Authors

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

Affiliations

Soon will be listed here.

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)-α production, with plasma concentrations of IFN-α that greatly (60- to 100-fold) exceed those seen in other viral infections, but little IFN-β 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-β therapy in filovirus infection. Here we show that early postexposure treatment with IFN-β 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-β also significantly increased survival time after Marburg virus infection. IFN-β may have promise as an adjunctive postexposure therapy in filovirus infection.

Citing Articles

An update on nonhuman primate usage for drug and vaccine evaluation against filoviruses.

de La Vega M, Xiii A, Massey S, Spengler J, Kobinger G, Woolsey C Expert Opin Drug Discov. 2024; 19(10):1185-1211.

PMID: 39090822 PMC: 11466704. DOI: 10.1080/17460441.2024.2386100.

Post-exposure intranasal IFNα suppresses replication and neuroinvasion of Venezuelan Equine Encephalitis virus within olfactory sensory neurons.

Cain M, Klein N, Jiang X, Salimi H, Wu Q, Miller M J Neuroinflammation. 2024; 21(1):24.

PMID: 38233868 PMC: 10792865. DOI: 10.1186/s12974-023-02960-1.

Ebola virus VP35 perturbs type I interferon signaling to facilitate viral replication.

Cao Z, Liu C, Peng C, Ran Y, Yao Y, Xiao G Virol Sin. 2023; 38(6):922-930.

PMID: 37839549 PMC: 10786653. DOI: 10.1016/j.virs.2023.10.004.

Computed Tomography Imaging for Monitoring of Marburg Virus Disease: a Nonhuman Primate Proof-Of-Concept Study.

Sword J, Lee J, Castro M, Solomon J, Aiosa N, Reza S Microbiol Spectr. 2023; 11(3):e0349422.

PMID: 37036346 PMC: 10269526. DOI: 10.1128/spectrum.03494-22.

Interferon therapy and its association with depressive disorders - A review.

Lai J, Ho J, Kow A, Liang G, Tham C, Ho Y Front Immunol. 2023; 14:1048592.

PMID: 36911685 PMC: 9992192. DOI: 10.3389/fimmu.2023.1048592.

References

Halfmann P, Neumann G, Kawaoka Y . The Ebolavirus VP24 protein blocks phosphorylation of p38 mitogen-activated protein kinase. J Infect Dis. 2011; 204 Suppl 3:S953-6. PMC: 3189987. DOI: 10.1093/infdis/jir325. View

Larsen T, Stevens E, Davis K, Geisbert J, Daddario-DiCaprio K, Jahrling P . Pathologic findings associated with delayed death in nonhuman primates experimentally infected with Zaire Ebola virus. J Infect Dis. 2007; 196 Suppl 2:S323-8. DOI: 10.1086/520589. View

Basler C, Amarasinghe G . Evasion of interferon responses by Ebola and Marburg viruses. J Interferon Cytokine Res. 2009; 29(9):511-20. PMC: 2988466. DOI: 10.1089/jir.2009.0076. View

Raymond J, Bradfute S, Bray M . Filovirus infection of STAT-1 knockout mice. J Infect Dis. 2011; 204 Suppl 3:S986-90. DOI: 10.1093/infdis/jir335. View

Gupta M, Mahanty S, Ahmed R, Rollin P . Monocyte-derived human macrophages and peripheral blood mononuclear cells infected with ebola virus secrete MIP-1alpha and TNF-alpha and inhibit poly-IC-induced IFN-alpha in vitro. Virology. 2001; 284(1):20-5. DOI: 10.1006/viro.2001.0836. View

Perou C, Sorlie T, Eisen M, van de Rijn M, Jeffrey S, Rees C . Molecular portraits of human breast tumours. Nature. 2000; 406(6797):747-52. DOI: 10.1038/35021093. View

Geisbert T, Geisbert J, Leung A, Daddario-DiCaprio K, Hensley L, Grolla A . Single-injection vaccine protects nonhuman primates against infection with marburg virus and three species of ebola virus. J Virol. 2009; 83(14):7296-304. PMC: 2704787. DOI: 10.1128/JVI.00561-09. View

Bray M, Geisbert T . Ebola virus: the role of macrophages and dendritic cells in the pathogenesis of Ebola hemorrhagic fever. Int J Biochem Cell Biol. 2005; 37(8):1560-6. DOI: 10.1016/j.biocel.2005.02.018. View

Baize S, Leroy E, Georges-Courbot M, Capron M, Debre P, Fisher-Hoch S . Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients. Nat Med. 1999; 5(4):423-6. DOI: 10.1038/7422. View

10.

Geisbert T, Hensley L, Larsen T, Young H, Reed D, Geisbert J . Pathogenesis of Ebola hemorrhagic fever in cynomolgus macaques: evidence that dendritic cells are early and sustained targets of infection. Am J Pathol. 2003; 163(6):2347-70. PMC: 1892369. DOI: 10.1016/S0002-9440(10)63591-2. View

11.

Rubins K, Hensley L, Wahl-Jensen V, Daddario DiCaprio K, Young H, Reed D . The temporal program of peripheral blood gene expression in the response of nonhuman primates to Ebola hemorrhagic fever. Genome Biol. 2007; 8(8):R174. PMC: 2375004. DOI: 10.1186/gb-2007-8-8-r174. View

12.

Li L, Sherry B . IFN-alpha expression and antiviral effects are subtype and cell type specific in the cardiac response to viral infection. Virology. 2009; 396(1):59-68. PMC: 2787694. DOI: 10.1016/j.virol.2009.10.013. View

13.

Smith D, Johnson B, Isaacson M, Swanapoel R, Johnson K, Killey M . Marburg-virus disease in Kenya. Lancet. 1982; 1(8276):816-20. DOI: 10.1016/s0140-6736(82)91871-2. View

14.

Monath T, Brinker K, CHANDLER F, Kemp G, Cropp C . Pathophysiologic correlations in a rhesus monkey model of yellow fever with special observations on the acute necrosis of B cell areas of lymphoid tissues. Am J Trop Med Hyg. 1981; 30(2):431-43. DOI: 10.4269/ajtmh.1981.30.431. View

15.

Geisbert T, Hensley L . Ebola virus: new insights into disease aetiopathology and possible therapeutic interventions. Expert Rev Mol Med. 2004; 6(20):1-24. DOI: 10.1017/S1462399404008300. View

16.

Walker D, McCormick J, Johnson K, WEBB P, ELLIOTT L, Gardner J . Pathologic and virologic study of fatal Lassa fever in man. Am J Pathol. 1982; 107(3):349-56. PMC: 1916239. View

17.

Eden E, Navon R, Steinfeld I, Lipson D, Yakhini Z . GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists. BMC Bioinformatics. 2009; 10:48. PMC: 2644678. DOI: 10.1186/1471-2105-10-48. View

18.

Dillman 3rd J, Phillips C . Comparison of non-human primate and human whole blood tissue gene expression profiles. Toxicol Sci. 2005; 87(1):306-14. DOI: 10.1093/toxsci/kfi243. View

19.

Villinger F, Rollin P, Brar S, Chikkala N, Winter J, Sundstrom J . Markedly elevated levels of interferon (IFN)-gamma, IFN-alpha, interleukin (IL)-2, IL-10, and tumor necrosis factor-alpha associated with fatal Ebola virus infection. J Infect Dis. 1999; 179 Suppl 1:S188-91. DOI: 10.1086/514283. View

20.

Masuyama T, Matsuo M, Ichimaru T, Ishii K, Tsuchiya K, Hamasaki Y . Possible contribution of interferon-alpha to febrile seizures in influenza. Pediatr Neurol. 2002; 27(4):289-92. DOI: 10.1016/s0887-8994(02)00452-6. View