A novel approach using IFNAR1 KO mice for assessing Akabane virus pathogenicity and vaccine efficacy

Akabane virus (AKAV) is a Simbu serogroup virus that can cause congenital abnormalities in ruminants. In 2010, an AKAV-7 strain exhibiting different characteristics and belonging to a distinctive genogroup compared to previous AKAVs was isolated in South Korea. Although this novel pathogenic AKAV-7 has been discovered, in vivo studies on AKAV-7 are currently insufficient due to limitations of using large animals and suckling mice. Therefore, the development of a novel small animal model for AKAV studies is necessary. Type I interferon receptor knock out (IFNAR1 KO) mice are widely employed as an infection model for Bunyavirales viruses. Here, we evaluated the suitability of IFNAR1 KO mice as a small animal model for AKAV infection. IFNAR1 KO mice inoculated with AKAV-7 strain by intraperitoneal (IP) and subcutaneous (SC) routes showed 100% mortality with high viral loads in organs and histopathological changes in the spleen and liver. These findings suggest that IFNAR1 KO mouse is susceptible to AKAV-7 infection and suitable for use as a uniformly lethal mouse model of AKAV-7. Furthermore, IFNAR1 KO mice vaccinated with the AKAV vaccine showed full protection against AKAV-7 challenge, suggesting that IFNAR1 KO mice might be useful as an animal model for AKAV vaccine studies.