Ecological factors and genetic features are associated with ecological generalism in pathogenic tick-borne viruses.

Emerging and re-emerging tick-borne viruses (TBVs) have caused numerous outbreaks recently, yet the factors driving their emergence and pathogenicity in humans remain poorly understood across viral taxa. A large-scale analysis integrating epidemiological and genomic data of pathogenic TBVs reveal that highly pathogenic TBVs (HPTBVs) tend to exhibit ecological generalism. Specifically, HPTBVs infect a broader range of tick species, animal hosts, and ecotypes, which likely enhance their transmission to humans. Bird migration is identified as the primary driver for geographic spread of HPTBVs through modeling and phylogeographic analyses, while livestock density and TBVs' diversity they carry determine HPTBVs local persistence. HPTBVs experience stronger positive selection in genes related to host interactions, with specific mutations associated with lineage adaptation. Notably, the positively selected D170N mutation in severe fever with thrombocytopenia syndrome virus is predicted to be an enhanced binding affinity to human receptors, which correlate with increased infectivity. In this work, using TBV as a model system, we verify our hypothesis that ecological generalism is associated with increased pathogenicity and adaptability. These findings highlight the ecological and evolutionary mechanisms that drive the generalization of TBV and underscore their potential implications for public health risk.