Phylogenetic and biological features of severe fever with thrombocytopenia syndrome virus from multi-species infections in eastern China

Severe fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV), is an emerging tick-borne disease with high mortality and complex transmission dynamics. Since its first identification in China, SFTS has become an endemic infectious disease with continuously expanding geographic distribution and increasing incidence, posing a growing public health concern. In this study, we performed multi-species surveillance, virus isolation, whole-genome sequencing, and phenotypic characterization of 24 SFTSV strains obtained from humans, ticks, and fur-bearing animals in Shandong Province between 2024 and 2025. Phylogenetic analysis revealed co-circulation of four genotypes, with genotype D predominating, and identified eight reassortment and eight recombination events, indicating active genomic reshuffling. Comparative genomic analysis demonstrated high similarity between human- and fur animal-derived SFTSV, suggesting potential cross-species transmission. In vitro experiments further confirmed genotype-dependent replication efficiency, with genotype D exhibiting significantly superior viral proliferation. Collectively, these findings highlight the complex genetic diversity, evolutionary dynamics, and multi-species transmission potential of SFTSV, emphasizing the need for integrated genomic and phenotypic surveillance to inform public health interventions. IMPORTANCE Severe fever with thrombocytopenia syndrome virus (SFTSV) continues to cause sporadic and clustered infections in East Asia, but its mechanisms of interspecies transmission and local evolution remain poorly defined. This study represents one of the most comprehensive multi-host investigations of SFTSV in eastern China, integrating laboratory diagnosis, genomic surveillance, and biological characterization. By isolating and comparing viral strains from humans, ticks, and fur-bearing animals, we demonstrate genotype-dependent replication efficiency and provide molecular evidence for direct animal-to-human transmission. These findings expand the understanding of SFTSV ecology and evolution, underscore the diagnostic value of multi-source sample testing, and highlight the need for integrated “One Health” surveillance strategies to prevent zoonotic spillover and human infection.