Genotype-Dependent Virulence of Severe Fever with Thrombocytopenia Syndrome Virus in a Mouse Challenge Model

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with high case-fatality rates in East Asia. The causative agent, SFTS virus (SFTSV; also known as Dabie bandavirus), exhibits genotype-dependent differences in pathogenicity. However, infection models that recapitulate these variations and can be applied for vaccine and therapeutic evaluation are still lacking. In this study, we assessed the pathogenicity of two Korean SFTSV isolates representing the F and B genotypes in a murine infection model. Wild-type C57BL/6 and IFNAR knockout (IFNAR−/−) mice were intraperitoneally infected with two different doses of SFTSV (2 and 2 × 10−1 FFU). All C57BL/6 mice survived regardless of viral genotype or dose. In IFNAR−/− mice, infection with either F- or B-type virus at the 2 FFU dose resulted in mortality beginning at 5 days post-infection, with all mice succumbing within 6 days. At the higher dose (2 × 10−1 FFU), mortality differed by genotype: B-type infection led to 20% lethality, whereas F-type infection caused 40% lethality by day 5. Infected and deceased mice exhibited body weight loss as a characteristic clinical outcome. Collectively, these findings demonstrate genotype-associated differences in SFTSV pathogenicity in mice and establish a murine challenge model that may be useful for the preclinical evaluation of candidate vaccines and antiviral agents.