Assessment of three antiviral compounds against Borealpox virus infection in a mouse model

Borealpox virus (BRPV) is a zoonotic orthopoxvirus which was first documented in Alaska in 2015. Although most human infections are mild, a recent fatal case in an immunocompromised individual highlights the importance of studying this emerging pathogen. To date, less than 10 human cases of BRPV infection have been confirmed which limit the availability of clinical data on the effectiveness of antiviral therapy. Here, we examined the effectiveness of cidofovir, brincidofovir, and tecovirimat in cell culture and found all three were potent inhibitors of BRPV. In order to further study these modalities in vivo, we assessed immunocompetent and immunodeficient mice as disease models for BRPV. CAST/EiJ mice proved to be a suitable immunocompetent model for BRPV infection with high viral titres in several organs and route-dependent lethality. BRPV infection in immunodeficient mice, including STAT1^-/-, scid, and NSG strains, was uniformly lethal and characterized by high viral titres as well as profuse fluid retention in the peritoneal cavity. Using CAST/EiJ mice, we then evaluated cidofovir, brincidofovir, and tecovirimat therapies. Post-exposure treatment resulted in significant reductions in viral titres and an improved clinical course of infection. Our results demonstrate the utility of mouse models to study the pathogenicity of BRPV and support the use of these antivirals to treat human infections.