Development of a Murine Model for Aerosolized Ebolavirus Infection Using a Panel of Recombinant Inbred Mice

摘要: Countering aerosolized filovirus infection is a major priority of biodefense research. Aerosol models have been developed in knock-out mice, guinea pigs and non-human primates; however, immunocompetent mice by the aerosol route has not reported. A murine model should be useful for screening vaccine candidates therapies. In this study, various strains wild-type immunocompromised were exposed to (WT) or mouse-adapted (MA) Ebola virus (EBOV). Upon exposure WT-EBOV, BALB/c, C57BL/6 (B6), DBA/2 (D2) unaffected, but 100% severe combined immunodeficiency (SCID) 90% signal transducers activators transcription (Stat1) (KO) became moribund between 7–9 days post-exposure (dpe). Exposure MA-EBOV caused 15% body weight loss all recovered. contrast, 10–30% lethality was observed B6 D2 MA-EBOV, SCID, Stat1 KO, interferon (IFN)-γ KO Perforin 7–14 dpe. order identify wild-type, inbred, mouse which uniformly lethal, 60 BXD (C57BL/6 crossed with DBA/2) recombinant inbred (RI) advanced RI (ARI) monitored disease severity. complete spectrum severity observed. All lost many However, lethal within 7 12 five strains. these 10-fold less resulted ranging from 0% two 90–100% Analysis post-mortem tissue that euthanized at lower dose showed liver damage as well lung lesions three The exhibited mortality, even low airborne will testing vaccines Additionally, since susceptibility affected complex genetic traits, systems genetics approach used preliminary gene loci modulating among panel Preliminary quantitative trait (QTLs) identified are likely harbor genes involved differential infection.