A novel tick-borne phlebovirus, closely related to severe fever with thrombocytopenia syndrome virus and Heartland virus, is a potential pathogen

Abstract

Tick-borne viral diseases have attracted much attention in recent years because of their increasing incidence and threat to human health. Severe fever with thrombocytopenia syndrome phlebovirus (SFTSV) and Heartland virus (HRTV) were recently identified as tick-borne phleboviruses (TBPVs) in Asia and the United States, respectively, and are associated with severe human diseases with similar clinical manifestations. In this study, we report the first identification and isolation of a novel TBPV named Guertu virus (GTV) from Dermacentor nuttalli ticks in Xinjiang Province, China, where TBPVs had not been previously discovered. Genome sequence and phylogenetic analyses showed that GTV is closely related to SFTSV and HRTV and was classified as a member of the genus Phlebovirus, family Phenuiviridae, order Bunyavirales. In vitro and in vivo investigations of the properties of GTV demonstrated that it was able to infect animal and human cell lines and can suppress type I interferon signaling, similar to SFTSV, that GTV nucleoprotein (NP) can rescue SFTSV replication by replacing SFTSV NP, and that GTV infection can cause pathological lesions in mice. Moreover, a serological survey identified antibodies against GTV from serum samples of individuals living in Guertu County, three of which contained neutralizing antibodies, suggesting that GTV can infect humans. Our findings suggested that this virus is a potential pathogen that poses a threat to animals and humans. Further studies and surveillance of GTV are recommended to be carried out in Xinjiang Province as well as in other locations.

Acknowledgements

This work was supported by the Science and Technology Basic Work Program (2013FY113500) from the Ministry of Science and Technology of China, the National Science Foundation of China (no. 81760365), the European Union’s Horizon 2020 Research and Innovation Programme (no. 653316), and the Intergovernmental Special Program of State Key Research and Development Plan from the Ministry of Science and Technology of China (2016YFE0113500). We thank the Core Facility and Technical Support facility of the Wuhan Institute of Virology for the technical assistance.

Authors contributions

Yu.Z., T.L., A.M., A.A., and C.W. collected the tick samples and performed the morphological classification of ticks. X.D., Z.S., S.T., and Sh.S. grouped the ticks and prepared the homogenates. C.C. and Sh.S. performed the molecular classification of ticks. L.Z. conducted the Roche 454 sequencing. J.W. and Sh.S. analyzed the data. X.D. and Sh.S. isolated and identified the virus, obtained the complete sequence, and investigated the virus infection in different cells. Sh.S. performed the phylogenetic analyses. Sh.S. and L.Z. purified the virus and performed EM analyses. B.W. developed the SFTSV minigenome system, established the real-time RT-PCR methods, and examined GTV suppression of type I IFN signaling. L.Z. performed the experiments involving the GTV NP rescue of SFTSV NP, characterized GTV NSs-induced IBs, and cross-neutralization tests. Ya.Z. performed the growth curve analysis. C.K. and X.D. investigated the prevalence of GTV in ticks. C.L., Sh.S., Y.Z., S.T., and D.L. conducted the animal experiments and related tests. Su.S. and Yu.Z. collected the human serum samples. J.Z. and Sh.S. performed the serological studies with human samples. J.Q. prepared the anti-SFTSV Gn polyclonal antibody. F.D. and Sh.S. conceived of the study. Sh.S. analyzed all of the work and wrote the manuscript. H.W., Zh.H, Yu.Z., Su.S., and F.D. reviewed and finalized the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Supplementary Information accompanies this paper at (10.1038/s41426-018-0093-2).