Ticks are crucial vectors for various pathogens associated with human and animal diseases, including viruses. Nevertheless, significant knowledge gaps prevail in our understanding of tick-borne viruses (TBVs). We here examined existing studies on TBVs, uncovering 870 documented virus species across 28 orders, 55 families, and 66 genera. The discovery history, vector ticks, and hosts of TBVs, as well as the clinical characteristics of TBV-induced diseases, are summarized. In total, 176 tick species from nine tick genera were confirmed as vectors for TBVs. Overall, 105 TBVs were associated with infection or exposure to humans and animals. Of them, at least 40 were identified to cause human or animal diseases. This review addresses the current challenges associated with TBV research, including the lack of knowledge about the identification of novel and emerging TBVs, the spillover potentials from ticks to hosts, and the pathogenicity and infection mechanisms of TBVs. It is expected to provide crucial insights and references for future studies in this field, while specifically focusing on expanding surveys, improving TBV identification and isolation, and enhancing the understanding of TBV–vector–host interactions. All of these findings will facilitate the preparation for preventing and treating diseases caused by emerging and novel TBVs.

Guertu virus (GTV) is a tick-borne phleboviruses (TBPVs) which belongs to the genus Banyangvirus in the family of Phenuiviridae. In vitro and in vivo studies of GTV demonstrated that it was able to infect animal and human cell lines and could cause pathological lesions in mice. Glycoproteins (GP, including Gn and Gc) on the surface of Guertu virus (GTV) could bind to receptors on host cells and induce protective immunity in the host, but knowledge is now lacking on the information of B cell epitopes (BCEs) present on GTV-GP protein. The aim of this study was to identify all BCEs on Gn of the GTV DXM strain using rabbit pAbs against GTV-Gn. Seven fine BCEs and two antigenic peptides (APs) from nine reactive 16mer-peptides were identified, which are E_Gn1 (²PIICEGLTHS¹¹), E_Gn2 (¹³⁵CSQDSGT¹⁴¹), E_Gn3 (¹⁶⁵IP EDVF¹⁷⁰), E_Gn4 (¹⁶⁹VFQEL K¹⁷⁴), E_Gn5 (¹⁸⁷IDGILFN¹⁹³), E_Gn6 (²²³QTKWIQ²²⁸), E_Gn7 (²³⁷CHKDGIGPC²⁴⁵), AP-8 (²⁹⁹GVRVRPKCYGFSRMMA³¹⁴) and AP-9 (³⁵⁵CASH FCSSAESGKKNT³⁷⁰), of which six of mapped BCEs were recognized by the IgG-positive sheep serum obtained from sheep GTV-infected naturally. Multiple sequence alignments (MSA) based on each mapped BCE motif identified that the most of identified BCEs and APs are highly conserved among 10 SFTSV strains from different countries and lineages that share relatively close evolutionary relationships with GTV. The fine epitope mapping of the GTV-Gn would provide basic data with which to explore the GTV-Gn antigen structure and pathogenic mechanisms, and it could lay the foundation for the design and development of a GTV multi-epitope peptide vaccine and detection antigen.

Tick-borne viruses (TBVs) pose significant public health and economic threats. Pakistan has endemic Crimean-Congo hemorrhagic fever virus (CCHFV), but evidence suggests broader TBV circulation. This study assessed the seroprevalence of thirteen TBVs (seven are members of the genus Orthonairovirus and six are members of the genus Bandavirus) in humans, livestock, and rats in Punjab, Pakistan. Serum samples (n = 794: 321 livestock, 253 human, and 220 rat) were collected from the Narowal, Lahore, and Faisalabad districts. Antibodies to viral NPs were detected using the luciferase immunoprecipitation system (LIPS). The overall seroprevalence was 19.14% (152/794); it was highest in livestock (27.10%), then humans (20.55%), and then rats (5.91%). The highest seroprevalence rates were 3.12% for CCHFV in livestock, 3.56% for Yezo virus (YEZV) in humans, and 0.91% for Tamdy virus (TAMV) and Tacheng tick virus 1 (TcTV-1) in rats. Neutralizing antibodies were detected against CCHFV (1 cattle, 4 humans), Bhanja virus (BHAV) (3 livestock, 1 rat), TAMV (1 cattle), Guertu virus (GTV) (1 cattle), and Dabie bandavirus (2 cattle). Sixteen samples showed antibodies to both orthonairoviruses and bandaviruses, indicating co-exposure. Further analysis showed that seropositivity was not randomly distributed. Livestock kept in commercial farming systems and people working mainly outdoors had distinctly higher exposure to TBVs than subsistence livestock and indoor workers. The results supported the circulation of TBVs among hosts within the close socio-economic/ecological integration area of Pakistan. These findings confirm the circulation of CCHFV, SFTSV, GTV, and TAMV; provide the first serologic evidence of BHAV in Pakistan; and underscore the need for further investigation into the potential circulation of additional TBVs. All results demonstrated that multiple TBVs have been circulating among humans, livestock, and rodents in Pakistan.