Stat-1 knockout mice as a model for wild-type sudan virus (Sudv)

Olivier Escaffre, Terry L. Juelich, Natasha Neef, Shane Massey, Jeanon Smith, Trevor Brasel, Jennifer K. Smith, Birte Kalveram, Lihong Zhang, David Perez, Tetsuro Ikegami, Alexander N. Freiberg, Jason E. Comer

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Article number1388
JournalViruses
Volume13
Issue number7
DOIs
StatePublished - Jul 2021

Keywords

  • Animal model
  • Ebolavirus
  • Filovirus
  • STAT-1 knockout mice
  • SUDV

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

Fingerprint

Dive into the research topics of 'Stat-1 knockout mice as a model for wild-type sudan virus (Sudv)'. Together they form a unique fingerprint.

Cite this