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

Area of Science:

• Virology
• Immunology
• Infectious Diseases

Background:

• There is a critical need for FDA-licensed vaccines and therapeutics against Sudan ebolavirus (SUDV) infections, underscored by recent outbreaks.
• A well-characterized small animal model susceptible to wild-type filoviruses is essential for screening potential antivirals and vaccines.

Purpose of the Study:

• To determine the susceptibility of signal transducer and activator of transcription-1 knock out (STAT-1 KO) mice to various wild-type filoviruses.
• To characterize the SUDV infection model in STAT-1 KO mice for its utility in countermeasure development.

Main Methods:

• STAT-1 KO mice were infected with five different wild-type filoviruses: SUDV, Marburg virus (MARV), Zaire ebolavirus (EBOV), Bundibugyo ebolavirus (BDBV), and Taï Forest ebolavirus (TAFV).
• Lethality, viral load, hematological changes, and clinical chemistry were assessed.
• The efficacy of favipiravir as a potential countermeasure against SUDV was evaluated.

Main Results:

• SUDV and MARV were the most virulent filoviruses in STAT-1 KO mice, causing 100% and 80% lethality, respectively.
• SUDV infection in STAT-1 KO mice demonstrated lethality at low doses (3.1 × 10^1 pfu), with viral genomic material detectable in serum within 1-2 days post-challenge.
• Favipiravir treatment conferred complete protection against lethal SUDV challenge in STAT-1 KO mice.

Conclusions:

• STAT-1 KO mice are a valuable small animal model for studying filovirus infections, particularly SUDV.
• This model is suitable for the preclinical screening of antiviral drugs and vaccine candidates against SUDV.
• The susceptibility and pathological changes observed in STAT-1 KO mice closely mimic human filovirus infections, validating its use in countermeasure development.