Divergent virulence and serological profiles reveal pathogenic evolution within the <i>Bandavirus</i> genus

Viruses within the Bandavirus genus (Phenuiviridae family), phylogenetically divided into SFTSV and Bhanja groups, pose public health risks through cross-species transmission. Despite their significance, a systematic comparison of their infectivity, pathogenicity, and antigenicity is lacking. This study evaluates these key properties for five representative species: Severe fever with thrombocytopenia syndrome virus (SFTSV), Guertu virus (GTV), and Heartland virus (HRTV) from the SFTSV group; and Bhanja virus (BHAV) and Lone Star virus (LSV) from the Bhanja group. The five bandaviruses demonstrated efficient replication kinetics across a panel of human and mammalian cell lines, suggesting a broad cellular tropism. Wild-type C57BL/6 mice developed transient viremia (2–10 dpi) without overt disease, followed by neutralizing antibody production. Cross-neutralization was robust within each phylogenetic group but restricted between groups, supporting two separate serogroups. In contrast, IFNAR−/− C57BL/6 mice exhibited significant hematological abnormalities and uniformly lethal infection, with the 50% lethal dose–based virulence ranking as SFTSV > LSV > GTV >BHAV >HRTV. Pathological analysis revealed that SFTSV caused severe multi-organ damage, with predominant spleen tropism; GTV and HRTV induced similar but milder spleen-tropic lesions; and LSV and BHAV caused multi-organ injuries primarily affecting the liver and spleen. Our findings demonstrate that the variation in virulence among Bandavirus species is closely linked to their antigenic divergence and evolutionary lineages. The established infection models provide valuable platforms for investigating virus-host interactions and pathogenesis. These insights facilitate the development of vaccines and antiviral therapies, and improve public health preparedness against emerging tick-borne pathogens.