Search Results (166)

Ranges of distribution of some orthoflaviviruses, including the Omsk hemorrhagic fever virus (OHFV) and the Powassan virus (POWV), have been identified in the range endemic for the tick-borne encephalitis virus (TBEV). In contrast to TBEV, no registered vaccine against OHFV and POWV is currently available. Nevertheless, recent studies have indicated that the anti-TBEV vaccine may offer partial protection against other orthoflaviviruses. The present study assesses OHFV and POWV infection in an experimental model on BALB/c mice one, three- and twelve-months post-immunization with inactivated TBE vaccine. The TBE vaccine was shown to provide long-term protection against OHFV and partial protection against POWV, even in the absence of specific antibodies, and without indications of antibody-dependent enhancement of infection. The neutralizing antibody titer for OHFV in vaccinated animals before and after the challenge with OHFV was similar to the titer of antibodies against the TBEV vaccine strain. Following immunization with anti-TBEV vaccine and subsequent inoculation of POWV, the levels of neutralizing antibodies against the TBEV vaccine strain was observed to be higher compared to those targeting POWV, especially during the initial phase of infection. Such cross-reactive antibodies have potential to pose a significant diagnostic challenge in cases where an infection is occurring simultaneously with an immune response to another virus. Full article

Mechanisms of arboviral neuroinvasion are still incompletely resolved, despite longstanding emphasis on the blood-brain barrier (BBB) as the principal interface for central nervous system (CNS) entry. While BBB-centered models have been highly informative, they may underrepresent the contribution of other CNS border structures, particularly the choroid plexus and the blood-cerebrospinal fluid barrier (BCSFB). Here, we re-examine the BCSFB as a relevant but unevenly supported neuroinvasion interface in arboviral encephalitis. The strongest direct evidence is currently available for Zika virus (ZIKV), for which experimental studies support infection of choroid plexus-associated cells and CNS access through the blood-CSF axis. Semliki Forest virus (SFV) provides additional direct, although still limited, support for this concept. In contrast, for West Nile virus (WNV), Japanese encephalitis virus (JEV), and tick-borne encephalitis virus (TBEV), evidence for choroid plexus involvement remains indirect or insufficiently resolved, even though neuroinvasion itself is well established. We therefore argue not for replacement of BBB-centered models, but for broader integration of the BCSFB into current frameworks of arboviral CNS invasion. This evidence-based perspective supports a hierarchical, virus-dependent view of choroid plexus involvement and highlights the need for mechanistic studies that directly test when and how this interface contributes to encephalitic disease. Full article

Tick-borne encephalitis (TBE) is an emerging vector-borne disease in Europe, but its epidemiology remains poorly defined in Serbia. In orthoflavivirus-endemic settings, diagnostic challenges may contribute to underrecognition of TBE, particularly among patients with suspected West Nile virus (WNV) infection. We conducted a multicenter retrospective study including patients hospitalized between 2018 and 2023 with suspected WNV neuroinvasive disease or viral encephalitis of unknown etiology. Serum samples were tested for TBEV-neutralizing antibodies using a microneutralization assay. Among 79 patients, TBEV-neutralizing antibodies were detected in four (5.1%). Most reactive cases occurred in patients initially classified as having suspected WNV-associated meningoencephalitis, while TBE had not been considered in the differential diagnosis at admission. These findings suggest that TBE may be underrecognized in Serbia and highlight the importance of confirmatory testing in orthoflavivirus-endemic settings. Strengthening clinical awareness and surveillance will be essential to better define the burden of TBE and inform prevention strategies. Full article

In this study, we combined computational predictions with experimental validation as a hybrid strategy to explore whether the E protein of tick-borne encephalitis virus (TBEV) possesses autoimmune potential. Using in silico homology searches, we identified two viral epitopes (evglekl and vtgtqgt) within the TBEV E protein that share sequence identity with fragments of the human proteins DNAH7 and CSMD2. Antibodies against these epitopes were detected in the plasma of a subset of patients after natural TBEV infection. Notably, no such antibodies were found in recipients of the Tick-E-Vac vaccine, indicating that the current vaccine does not induce cross-reactive humoral responses to these epitopes. Further computational analysis predicted that these epitopes could be presented by HLA class II molecules (alleles DRB1*09:01 and DRB1*07:01), which are known to be associated with autoimmune pathologies. Molecular dynamics simulations confirmed stable binding of the peptides within the HLA grooves, with favorable binding energies. These findings suggest a possible involvement of T-helper cells in the autoreactive process. Natural TBEV infection can give rise to antibodies against epitopes homologous to human proteins, particularly in genetically predisposed hosts. While such homology alone does not predict the onset of autoimmune disease, it represents a risk factor. Full article

Tick-borne encephalitis virus (TBEV) is a major arthropod-borne flavivirus responsible for severe neurological disease in humans across Europe and Asia. It is maintained in nature through complex interactions within ticks and between tick vectors, vertebrate hosts and environmental factors. This review summarizes current knowledge on TBEV–tick interactions, focusing on virus acquisition, dissemination, vector competence, and long-term persistence within tick vectors. TBEV is acquired by ticks during blood feeding on viremic hosts or through co-feeding transmission under experimental conditions. Transovarial transmission has also been reported, as indicated by the detection of infected larvae in nature, although its efficiency appears to be low and variable. Following ingestion, TBEV infects and replicates in the tick midgut before dissemination via the hemolymph to secondary tissues, including the salivary glands and reproductive organs, which are essential for viral persistence and transmission. Vector competence and capacity vary between tick species and are shaped by intrinsic and extrinsic factors. Although transstadial transmission and transovarial transmission contribute to long-term virus maintenance, their efficiency is generally low and variable. In vitro models, including tick cell lines, have provided valuable insights into virus–tick interactions. Nevertheless, important knowledge gaps remain, particularly in understanding early events at the tick–host interface and mechanisms underlying viral dissemination and persistence within ticks. Full article

Despite serological evidence of tick-borne encephalitis virus (TBEV) circulation in Belgian animals since 2007, confirmed autochthonous human infection was only first documented in 2020. We review the current national epidemiologic situation and investigate a household cluster of confirmed autochthonous cases identified in 2025. A cohabiting couple experienced a near-simultaneous onset of meningoencephalitis and tested positive for TBEV-specific IgM and IgG, with confirmation by PRNT90. One patient reported a recent tick bite, and both patients reported consumption of unpasteurized milk and goat cheese, suggesting possible alimentary transmission. The identification of Case 2, who lacked neurological symptoms at presentation and was only tested due to the index case, illustrates the risk of missed diagnoses and supports the notion that human TBEV infection is likely underdiagnosed in Belgium. These findings underscore the need to increase clinical awareness, strengthen surveillance, and reinforce prevention strategies. TBE should be considered in the differential diagnosis of patients presenting with non-specific fever or neurological syndromes such as meningoencephalitis, particularly during the spring-to-autumn tick activity season. Full article

Tick-borne encephalitis virus (TBEV) is primarily transmitted by Ixodes spp. and poses significant health risks, leading to morbidity and mortality in humans. Two of the five subtypes, Siberian and Far Eastern are known to circulate in Mongolia. In 2021, Ixodes persulcatus ticks were collected from Bulgan aimag (province) using flagging and dragging methods and subsequently screened for TBEV using PCR. Positive samples underwent sequencing using an Oxford Nanopore Technologies-based hybrid capture approach, resulting in two coding-complete TBEV genomes from separate tick pools. Phylogenetic analysis classified both genomes within the Siberian subtype, grouping them with other Mongolian sequences from I. persulcatus collected in 2014, 2020, 2021, and 2023. The study sequences, PX654173 and PX654174, showed high genetic similarity (99.9% and 99.8%, respectively) to the sequence PQ479142, obtained from I. persulcatus ticks in Selenge, Mongolia, in 2021. The estimated time to most recent common ancestor (TMRCA) of the Siberian genotype was approximately 981 CE (95% HPD: 646–1347) with the emergence of a distinct Mongolian clade of TBEV around 1888 CE (95% HPD: 1834–1934). These findings highlight the value of expanded whole-genome sequencing to improve our understanding of TBEV’s genetic diversity and evolutionary history in Central Asia. Full article

Background/Objectives: Tick-borne encephalitis (TBE) is the most important tick-borne viral central nervous system (CNS) infection in Europe and Asia. Since the introduction of a vaccine in Austria in the late 1970s, sero-epidemiological studies on the true incidence of tick-borne encephalitis virus (TBEV) infection in the population have been difficult, because it was not possible to distinguish between vaccine- and infection-induced antibodies. The goal of our study has been to analyze the sero-epidemiology of TBEV infections, vaccination protection rate, and manifestation index of the disease in the region of interest. Methods: Applying a newly developed anti-TBEV-NS1-IgG assay and the neutralization test, the protection and infection rates in blood donors of the Austrian Federal State of Upper Austria.It is one of the first areas in Austria, where the TBEV vaccine had been rolled out and broadly used. Samples from blood donors of all districts of the Federal State of Upper Austria were screened for anti-TBEV-IgG. Positive sera were differentiated for infection- and vaccine-induced antibodies. The results were matched with donor age, gender, and geographical origin. Results: 2162 samples were analyzed. A total of 87.0% of the blood donors tested showed anti-TBEV-IgG related to past TBEV vaccination. Within the unvaccinated group, a total of 13.3% of male and 9.9% of female blood donors exhibited anti-TBEV-NS1-IgG, indicating a past TBEV infection. The anti-TBE-NS1-IgG seroprevalence was determined at 74/100,000 for the whole population and at 594/100,000 in the non-vaccinated population. The manifestation index (MI) was calculated at 2.8%. The MI is defined as the probability or percentage of infected individuals who develop clinical symptoms of a disease. Conclusions: Our data provide evidence of a continuing high risk of TBEV infection in the Federal state of Upper Austria. The non-vaccinated population has an eightfold higher infection prevalence compared to the whole population. The MI of TBEV for severe infection seems lower as detailed in previous reports. Full article

Viral infections have been implicated in psychiatric outcomes through immune-mediated pathways. This 12-month prospective cohort study, designed as a pilot and hypothesis-generating investigation, compared psychiatric symptoms and inflammatory cytokine profiles in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), hepatitis C virus (HCV), and tick-borne encephalitis virus (TBEV), and explored their potential predictive value. Thirty-seven patients hospitalized with viral infections and 32 healthy controls were evaluated, acknowledging the limited sample size. Psychiatric interviews and the Hospital Anxiety and Depression Scale (HADS) were used for assessment. The study was divided into two stages. In Stage 1, during the acute infection, a psychiatric assessment was conducted, and cytokine levels were measured in the patients’ blood. In Stage 2, one year later, the psychiatric assessment was repeated. No significant differences were found in psychiatric diagnosis rates or symptom severity between infection groups, regardless of viral type or neuroinvasive capacity. However, these findings should be interpreted as preliminary given the limited sample size. Some cytokines, eg., interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), and soluble interleukin-2 receptor subunit alpha (sIL-2Rα), showed associations with individual symptoms, but these were inconsistent and did not demonstrate robust predictive value. Cluster analysis identified two distinct inflammatory profiles—one characterized by higher cytokine levels (predominantly in Coronavirus disease 2019 (COVID-19) and TBEV cases) and the other by lower cytokine levels (mostly in HCV and controls). However, different cytokine profiles did not correspond to clinical outcomes. The results suggest that psychiatric sequelae after viral infections are not directly driven by specific cytokines or infection type but rather emerge from a complex interaction of immune, psychological, and environmental factors. Single cytokine measurement is insufficient and cannot be used as a tool for assessing the risk of developing psychiatric disorders. Given the exploratory nature of the study, all results require confirmation in larger, adequately powered cohorts. Future studies should focus on composite biomarkers and systems-based models such as neuroimmune-metabolic-oxidative pathways (NIMETOX), or Immune-Inflammatory Response System (IRS)/Compensatory Immune Response System (CIRS)/Oxidative & Nitrosative Stress (O&NS) for improved predictive accuracy. Full article

Background/Objectives: While tick-borne encephalitis virus (TBEV) is genetically relatively conserved, the significant antigenic divergence between its main circulating subtypes hinders the development of broadly effective antiviral treatments and vaccines. Current inactivated TBEV vaccines offer limited cross-protection against heterologous strains, as evidenced by cases among vaccinated individuals in endemic regions. The aim of this study was to design a candidate mRNA vaccine and evaluate the breadth of protective immunity it elicits. Methods: Ten candidate mRNA-PrM/E-LNP vaccines were comparatively evaluated for immunogenicity and protective efficacy in BALB/c mice. Immunogenicity was assessed by measuring antigen-specific IgG titers via ELISA and neutralizing antibody titers against a panel of TBEV strains using a virus-neutralization test. Protective efficiency was determined in a lethal challenge model, where immunized mice were challenged with one of seven distinct TBEV strains. Results: Vaccination with all tested mRNA-PrM/E-LNP candidates conferred 100% survival in mice following a lethal challenge with each of the seven TBEV strains (100 LD₅₀). The construct mRNA-PrM/E—Krasny Yar-8 demonstrated the highest immunogenicity, inducing antigen-specific antibodies with a geometric mean titer (GMT) of 1:6625, as well as the broadest virus-neutralizing activity against both homologous and heterologous TBEV strains in vitro. Conclusions: The mRNA platform represents a promising strategy for developing TBEV vaccines, demonstrating high immunogenicity and cross-protective efficacy against diverse viral strains. Full article

Tick-borne encephalitis virus (TBEV) causes tick-borne encephalitis (TBE), a severe disease of the human central nervous system. Currently, the data on the genetic variants of TBEV in Kyrgyzstan are practically absent. Therefore, the aim of this study was to analyze and describe the genetic diversity of TBEV in this region. The complete genome sequences of seven TBEV strains from the collection of the Scientific Centre for Family Health and Human Reproduction Problems (Irkutsk, Russia) were determined. These strains, isolated from Ixodes persulcatus ticks from Kyrgyzstan, were sequenced using the next generation sequencing approach on a MiSeq high-performance sequencer (Illumina, San Diego, CA, USA). A molecular genetic analysis of the obtained sequences, along with sequences of two previously isolated TBEV strains from Kyrgyzstan available in the GenBank database, demonstrated that the Siberian subtype of three genetic lineages (Zausaev, Vasilchenko and Bosnia) is predominantly distributed in Kyrgyzstan. The Far Eastern subtype of TBEV is also present. To date, this location probably represents the southernmost boundary of these TBEV subtypes’ ranges. Full article

Background: Adrenomedullin (ADM) is a multifunctional peptide with vasoregulatory, antimicrobial, and anti-inflammatory properties. Its stable fragment, mid-regional pro-adrenomedullin (MR-proADM), is a validated biomarker in sepsis and systemic infections, but its role in viral neuroinfections remains unexplored. Tick-borne encephalitis (TBE), caused by the tick-borne encephalitis virus (TBEV), is a major viral infection of the central nervous system (CNS) associated with long-term neurological sequelae. This study aimed to assess MR-proADM levels in cerebrospinal fluid (CSF) and serum of patients with TBE and to evaluate their diagnostic utility and pathophysiological significance. Methods: This retrospective observational study included 20 patients with confirmed TBE and 14 non-infectious neurological controls. MR-proADM concentrations were measured in paired CSF and serum samples using an ELISA assay. Statistical analyses included group comparisons (Mann–Whitney U test), correlation analyses (Spearman’s r), and receiver operating characteristic (ROC) curve evaluation. Results: Serum MR-proADM levels at baseline (SER1) were significantly lower in TBE patients compared with controls (p = 0.0197). The CSF/serum MR-proADM ratio differed significantly between groups (p = 0.0063) and showed the best diagnostic performance (AUC = 0.816, 95% CI 0.63–0.93; sensitivity 79%, specificity 80%). MR-proADM concentrations in CSF correlated with total CSF protein (r = 0.53), suggesting an association with blood–CSF barrier dysfunction. Strong reproducibility was observed for serum MR-proADM between sampling points (r = 0.83). Conclusions: MR-proADM levels in CSF and serum are altered in patients with TBE, indicating its potential as a biomarker of CNS infection and inflammation. The CSF/serum MR-proADM ratio may serve as a sensitive indicator of blood–CSF barrier involvement, while decreased serum levels may reflect impaired systemic neuroprotective response. These findings highlight a possible role of ADM in neuroimmune regulation during viral encephalitis and warrant validation in larger prospective studies. Full article

Background: Latvia is one of the most endemic tick-borne encephalitis (TBE) countries in Europe. However, assessing TBE seroprevalence and true infection rates has been challenging. Current diagnostics cannot reliably distinguish between immune responses induced by natural infection from those induced by vaccination, especially in TBE endemic countries with recommended immunisation programmes. A recently developed ELISA targeting antibodies against TBEV non-structural protein 1 (NS1) offers improved specificity for natural infection and can differentiate among three clinically relevant TBEV subtypes. Methods: We conducted a cross-sectional TBEV seroprevalence study in the Latvian population during 2019–2022, consisting of two pools: 1020 residents living in different regions of Latvia and 200 random Latvian Biobank blood samples. We used the standard anti-TBEV IgG ELISA (VIDITEST, VIDIA, Czech Republic) for the screening and detection of TBEV (whole virus) IgG antibodies and the newly established research-use anti-TBEV NS1 IgG ELISA for the detection of subtype-specific TBEV NS1 IgG antibodies against three virus subtypes: European, Siberian and Far Eastern. Results: The total TBEV seroprevalence among 1020 residents was 39.7%, representing all age cohorts of the population from all regions of Latvia. In total, 33.4% of the enrolled population were vaccinated against TBE with at least one dose of the TBE vaccine. Among the unvaccinated population, 16.3% had positive TBEV-specific IgG antibodies by standard ELISA. On the contrary, NS1-specific antibodies, indicating past natural infection, were detected in only 4.3% of the overall study population. Subtype differentiation revealed infections from all three major TBEV subtypes present in Latvia. Conclusions: In conclusion, this population-based study highlights a high risk of TBE in Latvia, with substantial seroprevalence even among unvaccinated individuals. The NS1-based ELISA enhances the accuracy of TBE surveillance and offers important clinical utility by facilitating more reliable diagnosis and case classification, regardless of vaccination status. 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

Ticks are important parasites of economic and public health because of their ability to transmit zoonotic diseases. Tick-borne encephalitis virus (TBEV), now officially Orthoflavivirus encephalitidis, is a Flavivirus with five main subtypes of which three, the European (TBEV-EU), the Siberian (TBEV-Sib), and the Far-Eastern subtypes (TBEV-FE), are supposedly circulate in Latvia. Several hard tick species are involved in TBEV circulation and transmission in nature. This study set out to describe the genetic landscape of TBEV subtypes in Latvian tick populations. In 2019 and 2021 to 2023, a total of 3026 ticks were collected in three Latvian regions, with Ixodes ricinus as the dominant species (2822 specimens), followed by Ixodes persulcatus (200 specimens) and Dermacentor reticulatus (4 specimens). Ticks were morphologically identified, pooled, and screened for TBEV RNA by RT-qPCR. TBEV of positive tick pools were isolated and genetically characterized by genome sequencing. Our study demonstrates the prevalence of two TBEV subtypes in Latvia with specific spatial patterning. In the sympatric Vidzeme region, these subtypes display a preferential species association of TBEV-EU with Ixodes ricinus and TBEV-Sib with Ixodes persulcatus. Phylogeographic analysis suggests independent introductions of multiple genotypes from both subtypes. Further investigations are necessary to better understand the natural transmission and the medical importance of these TBEVs. Full article