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Article

STAT-1 Knockout Mice as a Model for Wild-Type Sudan Virus (SUDV)

by
Olivier Escaffre
1,
Terry L. Juelich
1,
Natasha Neef
2,
Shane Massey
3,
Jeanon Smith
3,
Trevor Brasel
3,4,5,
Jennifer K. Smith
1,
Birte Kalveram
1,
Lihong Zhang
1,
David Perez
6,
Tetsuro Ikegami
1,5,7,8,
Alexander N. Freiberg
1,5,7,8,* and
Jason E. Comer
3,4,5,9,*
1
Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
2
XTR Toxicologic Pathology Services LLC, Sterling, VA 20165, USA
3
Office of Regulated Nonclinical Studies, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
4
Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
5
The Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
6
Texas A&M University Division of Research, Texas A&M University, College Station, TX 77843, USA
7
Sealy Institute for Vaccine Sciences, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
8
Institute for Human Infections and Immunity, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
9
Institute of Translational Sciences, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
*
Authors to whom correspondence should be addressed.
Viruses 2021, 13(7), 1388; https://doi.org/10.3390/v13071388
Submission received: 18 June 2021 / Revised: 14 July 2021 / Accepted: 16 July 2021 / Published: 17 July 2021
(This article belongs to the Special Issue In Vivo Mouse Models of Human Viral Infections)
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Abstract

Currently there is no FDA-licensed vaccine or therapeutic against Sudan ebolavirus (SUDV) infections. The largest ever reported 2014–2016 West Africa outbreak, as well as the 2021 outbreak in the Democratic Republic of Congo, highlight the critical need for countermeasures against filovirus infections. A well-characterized small animal model that is susceptible to wild-type filoviruses would greatly add to the screening of antivirals and vaccines. Here, we infected signal transducer and activator of transcription-1 knock out (STAT-1 KO) mice with five different wildtype filoviruses to determine susceptibility. SUDV and Marburg virus (MARV) were the most virulent, and caused 100% or 80% lethality, respectively. Zaire ebolavirus (EBOV), Bundibugyo ebolavirus (BDBV), and Taï Forest ebolavirus (TAFV) caused 40%, 20%, and no mortality, respectively. Further characterization of SUDV in STAT-1 KO mice demonstrated lethality down to 3.1 × 101 pfu. Viral genomic material was detectable in serum as early as 1 to 2 days post-challenge. The onset of viremia was closely followed by significant changes in total white blood cells and proportion of neutrophils and lymphocytes, as well as by an influx of neutrophils in the liver and spleen. Concomitant significant fluctuations in blood glucose, albumin, globulin, and alanine aminotransferase were also noted, altogether consistent with other models of filovirus infection. Finally, favipiravir treatment fully protected STAT-1 KO mice from lethal SUDV challenge, suggesting that this may be an appropriate small animal model to screen anti-SUDV countermeasures.
Keywords: ebolavirus; filovirus; SUDV; STAT-1 knockout mice; animal model ebolavirus; filovirus; SUDV; STAT-1 knockout mice; animal model

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MDPI and ACS Style

Escaffre, O.; Juelich, T.L.; Neef, N.; Massey, S.; Smith, J.; Brasel, T.; Smith, J.K.; Kalveram, B.; Zhang, L.; Perez, D.; et al. STAT-1 Knockout Mice as a Model for Wild-Type Sudan Virus (SUDV). Viruses 2021, 13, 1388. https://doi.org/10.3390/v13071388

AMA Style

Escaffre O, Juelich TL, Neef N, Massey S, Smith J, Brasel T, Smith JK, Kalveram B, Zhang L, Perez D, et al. STAT-1 Knockout Mice as a Model for Wild-Type Sudan Virus (SUDV). Viruses. 2021; 13(7):1388. https://doi.org/10.3390/v13071388

Chicago/Turabian Style

Escaffre, Olivier, Terry L. Juelich, Natasha Neef, Shane Massey, Jeanon Smith, Trevor Brasel, Jennifer K. Smith, Birte Kalveram, Lihong Zhang, David Perez, and et al. 2021. "STAT-1 Knockout Mice as a Model for Wild-Type Sudan Virus (SUDV)" Viruses 13, no. 7: 1388. https://doi.org/10.3390/v13071388

APA Style

Escaffre, O., Juelich, T. L., Neef, N., Massey, S., Smith, J., Brasel, T., Smith, J. K., Kalveram, B., Zhang, L., Perez, D., Ikegami, T., Freiberg, A. N., & Comer, J. E. (2021). STAT-1 Knockout Mice as a Model for Wild-Type Sudan Virus (SUDV). Viruses, 13(7), 1388. https://doi.org/10.3390/v13071388

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