The diversity of emerging tick-borne viruses globally: From discoveries to zoonotic risk assessment

BACKGROUND: The increasing incidence and expanding geographic distribution of emerging tick-borne viruses (TBVs) threaten global health. However, the understanding of their diversity and human pathogenicity remains insufficient. METHODS: We conducted an exhaustive literature review from 1990 to 2024 to identify all emerging TBVs in vectors and hosts. We established TBV-tick host associations and predicted the zoonotic potential of TBVs to infect humans using an RNA polymerase composition-based model, which was further validated by testing patient samples. FINDINGS: Our analysis identified 230 emerging TBVs across 23 families within 15 orders. The Phenuiviridae family had the highest number of TBVs, while the Flaviviridae family exhibited the broadest host range and highest ratio of human-infective to non-human-infective viruses. Haemaphysalis longicornis and sheep carry the highest number of TBVs among vectors and animals, respectively. A total of 19 emerging TBVs were identified as causative agents of human infection, with viral members within the Nairoviridae and Flaviviridae families posing higher zoonotic potential. Among the 128 emerging TBVs that underwent zoonotic modeling, 25 were classified as very-high-risk for causing human infection. Validation confirmed three human-infective viruses: Sara tick phlebovirus (STPV), Dabieshan tick virus (DBTV), and Shanxi tick virus 2 (SXTV2) were detected in 3.13% (28), 0.33% (3), and 0.67% (6) of 896 patients in Northeastern China, respectively. CONCLUSIONS: We highlight TBV hotspots, priority vectors/hosts for surveillance, and high-risk viral families to mitigate zoonotic threats. FUNDING: This work was funded by the National Key Research and Development Program of China (2023YFC2604403) and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2020-12M-5-001).