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Viruses 2019, 11(2), 137; https://doi.org/10.3390/v11020137

Filovirus Virulence in Interferon α/β and γ Double Knockout Mice, and Treatment with Favipiravir

1
Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
2
Office of Regulated Nonclinical Studies, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
3
Sealy Institute for Vaccine Science, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
4
The Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
5
Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
6
Experimental Pathology Laboratories, Inc., Sterling, VA 20167, USA
7
Institute for Human Infections and Immunity, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
*
Author to whom correspondence should be addressed.
Received: 3 January 2019 / Revised: 25 January 2019 / Accepted: 30 January 2019 / Published: 3 February 2019
(This article belongs to the Collection Advances in Ebolavirus, Marburgvirus, and Cuevavirus Research)
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Abstract

The 2014 Ebolavirus outbreak in West Africa highlighted the need for vaccines and therapeutics to prevent and treat filovirus infections. A well-characterized small animal model that is susceptible to wild-type filoviruses would facilitate the screening of anti-filovirus agents. To that end, we characterized knockout mice lacking α/β and γ interferon receptors (IFNAGR KO) as a model for wild-type filovirus infection. Intraperitoneal challenge of IFNAGR KO mice with several known human pathogenic species from the genus Ebolavirus and Marburgvirus, except Bundibugyo ebolavirus and Taï Forest ebolavirus, caused variable mortality rate. Further characterization of the prototype Ebola virus Kikwit isolate infection in this KO mouse model showed 100% lethality down to a dilution equivalent to 1.0 × 10−1 pfu with all deaths occurring between 7 and 9 days post-challenge. Viral RNA was detectable in serum after challenge with 1.0 × 102 pfu as early as one day after infection. Changes in hematology and serum chemistry became pronounced as the disease progressed and mirrored the histological changes in the spleen and liver that were also consistent with those described for patients with Ebola virus disease. In a proof-of-principle study, treatment of Ebola virus infected IFNAGR KO mice with favipiravir resulted in 83% protection. Taken together, the data suggest that IFNAGR KO mice may be a useful model for early screening of anti-filovirus medical countermeasures. View Full-Text
Keywords: filovirus; Ebola virus; mouse; interferon receptor knockout filovirus; Ebola virus; mouse; interferon receptor knockout
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Comer, J.E.; Escaffre, O.; Neef, N.; Brasel, T.; Juelich, T.L.; Smith, J.K.; Smith, J.; Kalveram, B.; Perez, D.D.; Massey, S.; Zhang, L.; Freiberg, A.N. Filovirus Virulence in Interferon α/β and γ Double Knockout Mice, and Treatment with Favipiravir. Viruses 2019, 11, 137.

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