Search Results (5)

The Yezo virus (YEZV) is a recently discovered tick-borne orthonairovirus with pathogenic potential, causing acute febrile illness in humans. Viral nucleoproteins (N) play a key role in genome packaging, replication, and modulation of host immune responses, making their structural characterization essential for understanding viral pathogenesis and developing targeted countermeasures. However, the absence of structural data for YEZV proteins significantly hinders these efforts. This study presents the first solution structure of the YEZV N domain 1 (D1). A highly purified, soluble, tag-free recombinant YEZV N D1 was produced from the native sequence of the clinical YEZV isolate. The native-state conformation was resolved through an integrated approach combining size-exclusion chromatography coupled with small-angle X-ray scattering (SEC-SAXS), AlphaFold 3 structure prediction, and all-atom molecular dynamics simulations. The YEZV N D1 structure adopts a stable, predominantly α-helical globular fold that remains monomeric under near-physiological conditions. SEC-SAXS data show excellent agreement with computational models, revealing moderate conformational flexibility. The characterized recombinant YEZV N D1 and its first solution structure reported here providing essential insights into understanding of YEZV molecular architecture. These findings lay a foundation for rational serological assay development and structure-guided therapeutic design against this and other emerging orthonairoviruses. Full article

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. Full article

Ixodid ticks are blood-sucking ectoparasites of vertebrates. They constitute an integral part of natural foci and are responsible for the worldwide transmission of infections to humans, which can result in severe symptoms. For instance, the Tomsk region, where three abundant tick species (Dermacentor reticulatus, Ixodes pavlovskyi, I. persulcatus) occur, is an endemic area for tick-borne encephalitis virus (TBEV). An increasing number of novel infectious agents carried by ticks have been identified using metagenomic sequencing. A notable example is the Yezo virus (Orthonairovirus yezoense, YEZV), which was discovered in patients with fever after tick bites in Japan and China between 2014 and 2025. For the first time, we have performed metagenomic sequencing of the virome of ticks collected in the Tomsk region. In a sample obtained from a pool of I. pavlovskyi ticks, all three segments of the YEZV genome were detected. The phylogenetic analysis showed that the newly identified isolate formed a sister group to previously described virus isolates, indicating the presence of a new genetic variant. This study presents the first report of YEZV detection in I. pavlovskyi ticks in the Tomsk region, thereby expanding the geographical range and number of vector species for YEZV and highlighting the importance of monitoring viral agents circulating among ticks in Western Siberia. Full article

The recent discovery of the Yezo virus (YEZV) in Japan and China has raised particular concern due to its potential to cause human diseases ranging from mild febrile illnesses to severe neurological disorders. We report, for the first time, the detection of five YEZV isolates in I. persulcatus ticks from three regions of Russia. The analysis was performed using 5318 ticks of two Ixodes genus collected in 2024 from 23 regions of Russia. The minimum infection rate of YEZV in Russia among I. persulcatus ticks was 0.12% (95% CI: 0.05–0.28). The westernmost and northernmost YEZV detection points have been recorded. YEZV isolates circulating in Russia are genetically diverse. Protein domains of Russian YEZV isolates’ genomes were characterized using HMMER, AlphaFold 3, and InterProScan. The YEZV nucleoprotein (N) of Russian isolates has a racket-shaped structure with “head” and “stalk” domains similar to those of Orthonairovirus haemorrhagiae. The Lys261–Arg261 substitution in the YEZV N Chita 2024-1 isolate occurs in the α11 structure in the region of interaction with viral RNA. Our results show that the distribution area of YEZV is much wider than previously known, provide new data on complete YEZV genomes, extend our structural insight into YEZV N, and suggest a potential target for antiviral drug development to treat YEZV infection. Full article

A novel tick-borne orthonairovirus called the Yezo virus (YEZV), primarily transmitted by the Ixodes persulcatus tick, has been recently discovered and poses significant threats to human health. The YEZV is considered endemic in Japan and China. Clinical symptoms associated with this virus include thrombocytopenia, fatigue, headache, leukopenia, fever, depression, and neurological complications ranging from mild febrile illness to severe outcomes like meningitis and encephalitis. At present, there is no treatment or vaccine readily accessible for this pathogenic virus. Therefore, this research employed an immunoinformatics approach to pinpoint potential vaccine targets within the YEZV through an extensive examination of its structural proteins. Three structural proteins were chosen using specific criteria to pinpoint T-cell and B-cell epitopes, which were subsequently validated through interferon-gamma induction. Six overlapping epitopes for cytotoxic T-lymphocytes (CTL), helper T-lymphocytes (HTL), and linear B-lymphocytes (LBL) were selected to construct a multi-epitope vaccine, achieving a 92.29% coverage of the global population. These epitopes were then fused with the 50S ribosomal protein L7/L12 adjuvant to improve protection against international strains. The three-dimensional structure of the designed vaccine construct underwent an extensive evaluation through structural analysis. Following molecular docking studies, the YEZV vaccine construct emerged as a candidate for further investigation, showing the lowest binding energy (−78.7 kcal/mol) along with favorable physiochemical and immunological properties. Immune simulation and molecular dynamics studies demonstrated its stability and potential to induce a strong immune response within the host cells. This comprehensive analysis indicates that the designed vaccine construct could offer protection against the YEZV. It is crucial to conduct additional in vitro and in vivo experiments to verify its safety and effectiveness. Full article