Tick-borne encephalitis virus (TBEV) is a common virus in Europe and Asia, causing around 10,000 to 10,500 infections annually. It affects the central nervous system and poses threats to public health. However, the exact molecular mechanisms of TBE pathogenesis are not yet fully understood due to the complex interactions between the virus and its host. In this study, a comprehensive analysis was conducted to characterize the serum metabolome and proteome of adult patients infected with TBEV, in comparison to a control group of healthy individuals. Liquid chromatography tandem mass spectrometry (LC-MS) was employed to monitor metabolic and proteomic alternations throughout the progression of the disease, significant physiological changes associated with different stages of the disease were identified. A total of 44 proteins and 115 metabolites exhibited significantly alternations in the sera of patients diagnosed with TBE. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of these metabolites and proteins revealed differential enrichment of genes associated with the extracellular matrix, complement binding, hemostasis, lipid metabolism, and amino acid metabolism between TBE patients and healthy controls. We gained valuable understanding of the specific metabolites implicated in the host\'s responses to TBE, establishing a basis for further research on TBE disease. SIGNIFICANCE: The current investigation revealed a comprehensive and systematic differences on TBE using LC-MS platform from human serum samples of TBE patients and healthy individuals providing the immune response to the invasion of TBE.

Our aim was to examine the correlation between biomarkers of neuronal and glial cell damage and severity of disease in patients with tick-borne encephalitis.
One hundred and fifteen patients with tick-borne encephalitis diagnosed in Lithuania and Sweden were prospectively included, and cerebrospinal fluid (CSF) and serum samples were obtained shortly after hospitalization. Using pre-defined criteria, cases were classified as mild, moderate or severe tick-borne encephalitis. Additionally, the presence of spinal nerve paralysis (myelitis) and/or cranial nerve affection were noted. Concentrations of the brain cell biomarkers glial fibrillary acidic protein (GFAP), YKL-40, S100B, neurogranin, neurofilament light (NfL) and tau were analysed in CSF and, in addition, NfL, GFAP and S100B levels were measured in serum. The Jonckheere-Terpstra test was used for group comparisons of continuous variables and Spearman\'s partial correlation test was used to adjust for age.
Cerebrospinal fluid and serum concentrations of GFAP and NfL correlated with disease severity, independent of age, and with the presence of nerve paralysis. The markers neurogranin, YKL-40, tau and S100B in CSF and S100B in serum were detected, but their concentrations did not correlate with disease severity.
Neuronal cell damage and astroglial cell activation with increased NfL and GFAP in CSF and serum were associated with a more severe disease, independent of age. Increased GFAP and NfL concentrations in CSF and NfL in serum were also indicative of spinal and/or cranial nerve damage. NfL and GFAP are promising prognostic biomarkers in tick-borne encephalitis, and future studies should focus on determining the association between these biomarkers and long-term sequelae.

Tick-borne encephalitis virus (TBEV) is an enveloped RNA virus, a member of the genus Flavivirus (family Flaviviridae). Here, we provide a detailed analysis of the size and structure of the inactivated TBEV vaccine strain Sofjin-Chumakov. Four analytical methods were used to analyze individual TBEV particles-negative staining TEM, cryo-EM, atomic force microscopy (AFM), and nanoparticle tracking analysis (NTA). All methods confirmed that the particles were monodisperse and that their mean size was ~50 nm. Cryo-EM data allowed us to obtain a 3D electron density model of the virus with clearly distinguishable E protein molecules. STEM-EELS analysis detected phosphorus in the particles, which was interpreted as an indicator of RNA presence. Altogether, the described analytical procedures can be valuable for the characterization of inactivated vaccine virus samples.

Tick-borne encephalitis virus (TBEV) is a positive-sense single-stranded RNA virus belonging to the genus Flavivirus in Flaviviridae. It can cause the server infectious diseases named tick-borne encephalitis (TBE), which is characterized by paralysis and epilepsy. However, no effective treatment for TBE has been developed targeting TBEV. The NS3 helicase from TBEV plays an essential role in viral replication, which makes it an important target for drug design. In this study, the crystal structure of TBEV NS3 helicase has been determined to the resolution of 2.14 Å. Subsequent alignment with homologous structures reveals that the NTP binding site and RNA-binding sites are located in motifs Ⅱ and Ⅵ of NS3 and the critical residues for binding are conserved across species in the genus, while the distinct conformation transition implies that the TBEV helicase need a different local rearrangement. This study demonstrates the key atomic-level features of TBEV helicase and provides basis for the design of antiviral drugs targeting TBEV helicase.

Tick-borne encephalitis virus (TBEV) can cause fever, headache, neurological disorders, and/or peripheral flaccid paralysis; therefore, it is a major threat to public health. A rapid, sensitive, and simple method for detecting anti-TBEV antibodies is needed urgently to determine infection and for vaccine evaluation. Here, a luciferase-based immunocomplex assay system (Luc-IC) was developed to detect TBEV antibodies. The system is based on a reporter Nano luciferase (NLuc) that is co-expressed as a fusion protein with viral envelope domain III (ED3) in COS7 cells. The cell supernatant was used directly to detect antigen without the need for a purification step. This simple procedure effectively improved the sensitivity of the assay. Sera from 50 patients with an acute tick-borne encephalitis infection were tested to determine the sensitivity of the NLuc-IC assay. Furthermore, 62 sera from individuals infected with Japanese encephalitis virus, West Nile virus, yellow fever virus, dengue virus, or Zika virus were also tested to determine specificity. The results demonstrated that the assay was 100% sensitive and 100% specific for TBEV antibodies. Thus, this very simple NLuc-IC assay is potentially useful for rapid and accurate diagnosis of TBEV infection in both humans and animals.

Tick-borne encephalitis (TBE) is one of natural foci diseases transmitted by ticks. Its distribution and transmission are closely related to geographic and environmental factors. Identification of environmental determinates of TBE is of great importance to understanding the general distribution of existing and potential TBE natural foci. Hulunbuir, one of the most severe endemic areas of the disease, is selected as the study area. Statistical analysis, global and local spatial autocorrelation analysis, and regression methods were applied to detect the spatiotemporal characteristics, compare the impact degree of associated factors, and model the risk distribution using the heterogeneity. The statistical analysis of gridded geographic and environmental factors and TBE incidence show that the TBE patients mainly occurred during spring and summer and that there is a significant positive spatial autocorrelation between the distribution of TBE cases and environmental characteristics. The impact degree of these factors on TBE risks has the following descending order: temperature, relative humidity, vegetation coverage, precipitation and topography. A high-risk area with a triangle shape was determined in the central part of Hulunbuir; the low-risk area is located in the two belts next to the outside edge of the central triangle. The TBE risk distribution revealed that the impact of the geographic factors changed depending on the heterogeneity.

Tick-borne encephalitis (TBE) has become an increasing public health threat in recent years, ranging from Europe, through far-eastern Russia to Japan and northern China. However, the neglect of its expansion and scarce analyses of the dynamics have made the overall disease burden and the risk distribution of the disease being unclear in mainland China. In this study, we described epidemiological characteristics of 2117 reported human TBE cases from 2006 to 2013 in mainland China. About 99% of the cases were reported in forest areas of northeastern China, and 93% of reported infections occurred during May-July. Cases were primarily male (67%), mostly in 30-59 years among all age-gender groups. Farmers (31.6%), domestic workers (20.1%) and forest workers (17.9%) accounted for the majority of the patients, and the proportions of patients from farmers and domestic workers were increasing in recent years. The epidemiological features of TBE differed slightly across the affected regions. The distribution and features of the disease in three main endemic areas of mainland China were also summarized. Using the Boosted Regression Trees (BRT) model, we found that the presence of TBE was significantly associated with a composite meteorological index, altitude, the coverage of broad-leaved forest, the coverage of mixed broadleaf-conifer forest, and the distribution of Ixodes persulcatus (I. persulcatus) ticks. The model-predicted probability of presence of human TBE cases in mainland China was mapped at the county level. The spatial distribution of human TBE in China was largely driven by the distributions of forests and I. persulcatus ticks, altitude, and climate. Enhanced surveillance and intervention for human TBE in the high-risk regions, particularly on the forest areas in north-eastern China, is necessary to prevent human infections.