Molecular evolution and spatial transmission of severe fever with thrombocytopenia syndrome virus

Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging pathogen from the family Phenuiviridae, poses severe threats to public health in East Asia. In this study, we elucidate SFTSV's epidemiological dynamics, transmission patterns, and molecular determinants of virulence, through analysis of 1942 genomes obtained from multiple host species across endemic regions in China, South Korea, Japan, and Thailand (2005-2023). Phylogenetic reconstruction delineates two major lineages (L1-Chinese and L2-Japanese-Korean) comprising 13 genotypes (I-XIII). Viral diversity is shaped by extensive segment-specific reassortment (212 events, including L1-L1, L2-L2, and L1-L2 patterns) and recombination (69 events, 62 in China). The M segment exhibited significantly elevated recombination frequency compared to the L and S segments. Geographically, Hubei province in China emerges as a reassortment hotspot with exceptional genotype diversity, while Henan, Hubei, and Zhejiang provinces serve as key recombination centers. Bayesian phylogeographic analysis traces the origin of SFTSV to the Jiangsu-Anhui border region (~17th century). Subsequent spread occurred through two distinct transmission networks: the L1 lineage disseminated terrestrially from Jiangsu-Anhui/Shandong to the Dabie Mountains and Liaoning province, while the L2 lineage dispersed via marine routes, with South Korea acting as a key transmission hub. Integration of clinical data identifies five positively selected sites and mortality-associated co-mutation networks that are enriched in the genotype IV, which is associated with mortality.