Exploring the relationship between Lone Star Virus and Synaptogyrin-2 using novel viral and host models of infection

Authors: EATON, CHRISTIAN - University Of Nebraska-Lincoln; Walker, Lianna; VU, HIEP - University Of Nebraska-Lincoln; LOY, DUSTIN - University Of Nebraska-Lincoln; CIOBANU, DANIEL - University Of Nebraska-Lincoln

Submitted to: Vector-Borne and Zoonotic Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/15/2026
Publication Date: 2/4/2026
Citation: Eaton, C.W., Walker, L.R., Vu, H.L., Loy, D.J., Ciobanu, D.C. 2026. Exploring the relationship between Lone Star Virus and Synaptogyrin-2 using novel viral and host models of infection. Vector-Borne and Zoonotic Diseases. 0(0). https://doi.org/10.1177/15303667261420983.
DOI: https://doi.org/10.1177/15303667261420983

Interpretive Summary: Viruses transmitted by ticks, referred to as tick-borne viruses, pose an ongoing threat to animal and human health. For many of these viruses, little is known about how they survive within mammals or what factors influence disease outcomes following infection. This information is important for the development of effective preventative or therapeutic strategies. Scientists are working to identify closely related viruses associated with less severe disease and cell lines to serve as infection models to better understand and answer these questions. In this study, researchers developed a primate cell line using gene editing to explore how a cellular protein, known to interact with multiple viral pathogens, influences replication of the tick-borne Lone Star Virus (LSV) genome. While this protein has been shown to help another closely related tick-borne virus multiply in cells, disruption of this protein in primate cells did not have any effect on LSV replication. Therefore, these findings demonstrate a need to continue to investigate how different tick-borne viruses, even closely related viruses, infect mammals and cause disease.

Technical Abstract: Background: There is limited understanding of the replication and transmission of bandaviruses and the influence of host genotype in a successful infection. An in vitro bandavirus model, such as Lone Star Virus (LSV, Bandavirus amblyommae), capable of propagating in standard cell lines, could provide some of this critical information. In this study we sequenced the genome of LSV and profiled its relationship with a key host viral interacting protein (SYNGR2) known to influence replication of another member of bandaviruses, Dabie bandavirus. Materials and Methods: The genome of LSV TMA 1381 strain was sequenced and assembled using Oxford Nanopore Technology. The expression of SYNGR2 was profiled and annotated in Vero cells. SYNGR2 knock-out (KO) Vero clones were obtained via CRISPR-Cas9 gene editing targeting an exon present in all SYNGR2 isoforms. Following LSV infection, expression of SYNGR2 and LSV titer was measured in SYNGR2-KO and wild type cell lines. Results and Conclusions: Sequence variation and evidence of viral heterogeneity was detected across all segments of the LSV TMA 1381 strain. Important differences in the amino acid sequences of non-structural protein known to directly interact with host SYNGR2, was observed between LSV and other bandaviruses (15.5 to 47.4%). The change in SYNGR2 expression in wild type Vero cells was limited following LSV infection. No difference in LSV titer was detected between wild type and SYNGR2 KO Vero cells (P > 0.16). Our data illustrate key distinctions from previous bandavirus reports and underlines the need for future studies to explore the mechanisms of LSV replication, and pathogenesis.