{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:50:22Z","timestamp":1790272222400,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU Innovative Medicines Initiative (IMI) under Horizon2020 program for IM2PACT","award":["807015"],"award-info":[{"award-number":["807015"]}]},{"name":"EU Innovative Medicines Initiative (IMI) under Horizon2020 program for IM2PACT","award":["398066876\/GRK 2485\/2"],"award-info":[{"award-number":["398066876\/GRK 2485\/2"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["807015"],"award-info":[{"award-number":["807015"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["398066876\/GRK 2485\/2"],"award-info":[{"award-number":["398066876\/GRK 2485\/2"]}]},{"name":"Open Access Publication Fund of the University of Veterinary Medicine Hannover Foundation","award":["807015"],"award-info":[{"award-number":["807015"]}]},{"name":"Open Access Publication Fund of the University of Veterinary Medicine Hannover Foundation","award":["398066876\/GRK 2485\/2"],"award-info":[{"award-number":["398066876\/GRK 2485\/2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tick-borne encephalitis remains a significant burden on human health in the endemic areas in Central Europe and Eastern Asia. The causative agent, tick-borne encephalitis virus (TBEV), is a neurotropic virus belonging to the genus of Orthoflavivirus. After TBEV enters the central nervous system (CNS), it mainly targets neurons, causing encephalitis and leading to life-long disabilities, coma and, in rare cases, death. The neuroinvasive mechanisms of orthoflaviviruses are poorly understood. Here we investigate the mechanism of TBEV neuroinvasion, hypothesizing that TBEV influences blood\u2013brain barrier (BBB) properties and uses transcellular routes to cross the endothelial barrier and enter the CNS. To test this hypothesis, we employed an in vitro transwell system consisting of endothelial cell monolayers cultured on insert membranes and studied the barrier properties following inoculation to tick-borne orthoflaviviruses. It was shown that TBEV and closely related but naturally attenuated Langat virus (LGTV) crossed the intact endothelial cell monolayer without altering its barrier properties. Interestingly, transendothelial migration of TBEV was significantly affected when two cellular surface antigens, the laminin-binding protein and vimentin, were blocked with specific antibodies. Taken together, these results indicate that orthoflaviviruses use non-destructive transcellular routes through endothelial cells to establish infection within the CNS.<\/jats:p>","DOI":"10.3390\/ijms26052342","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T04:55:08Z","timestamp":1741236908000},"page":"2342","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Impact of Tick-Borne Orthoflaviviruses Infection on Compact Human Brain Endothelial Barrier"],"prefix":"10.3390","volume":"26","author":[{"given":"Felix","family":"Schweitzer","sequence":"first","affiliation":[{"name":"Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine, 30559 Hannover, Germany"},{"name":"Center for Systems Neuroscience (ZSN), 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6035-4009","authenticated-orcid":false,"given":"Tam\u00e1s","family":"Letoha","sequence":"additional","affiliation":[{"name":"Pharmacoidea Ltd., H-6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6535-3497","authenticated-orcid":false,"given":"Albert","family":"Osterhaus","sequence":"additional","affiliation":[{"name":"Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine, 30559 Hannover, Germany"},{"name":"Center for Systems Neuroscience (ZSN), 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6631-2096","authenticated-orcid":false,"given":"Chittappen Kandiyil","family":"Prajeeth","sequence":"additional","affiliation":[{"name":"Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0166-3542(02)00206-1","article-title":"Tick-Borne Encephalitis","volume":"57","author":"Gritsun","year":"2003","journal-title":"Antivir. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1016\/S0140-6736(08)60800-4","article-title":"Tick-Borne Encephalitis","volume":"371","author":"Lindquist","year":"2008","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"829","DOI":"10.20506\/rst.31.3.2167","article-title":"West Nile Virus Epidemiology and Factors Triggering Change in Its Distribution in Europe","volume":"31","author":"Pradier","year":"2012","journal-title":"Rev. Sci. Tech. Int. Off. Epizoot."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1093\/brain\/122.11.2067","article-title":"The Clinical and Epidemiological Profile of Tick-Borne Encephalitis in Southern Germany 1994\u201398: A Prospective Study of 656 Patients","volume":"122","author":"Kaiser","year":"1999","journal-title":"Brain"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1186\/s12974-020-01951-w","article-title":"Langat Virus Infection Affects Hippocampal Neuron Morphology and Function in Mice without Disease Signs","volume":"17","author":"Cornelius","year":"2020","journal-title":"J. Neuroinflam."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.antiviral.2019.01.014","article-title":"Tick-Borne Encephalitis in Europe and Russia: Review of Pathogenesis, Clinical Features, Therapy, and Vaccines","volume":"164","author":"Ruzek","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kubinski, M., Beicht, J., Gerlach, T., Volz, A., Sutter, G., and Rimmelzwaan, G.F. (2020). Tick-Borne Encephalitis Virus: A Quest for Better Vaccines against a Virus on the Rise. Vaccines, 8.","DOI":"10.3390\/vaccines8030451"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Petry, M., Palus, M., Leitzen, E., Mitterreiter, J.G., Huang, B., Kr\u00f6ger, A., Verjans, G.M.G.M., Baumg\u00e4rtner, W., Rimmelzwaan, G.F., and R\u016f\u017eek, D. (2021). Immunity to TBEV Related Flaviviruses with Reduced Pathogenicity Protects Mice from Disease but Not from TBEV Entry into the CNS. Vaccines, 9.","DOI":"10.1101\/2021.01.11.426200"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/2045-8118-10-16","article-title":"The hCMEC\/D3 Cell Line as a Model of the Human Blood Brain Barrier","volume":"10","author":"Weksler","year":"2013","journal-title":"Fluids Barriers CNS"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Dunton, A.D., G\u00f6pel, T., Ho, D.H., and Burggren, W. (2021). Form and Function of the Vertebrate and Invertebrate Blood-Brain Barriers. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212111"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Pulgar, V.M. (2019). Transcytosis to Cross the Blood Brain Barrier, New Advancements and Challenges. Front. Neurosci., 12.","DOI":"10.3389\/fnins.2018.01019"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.virol.2008.11.047","article-title":"West Nile Virus Infection Modulates Human Brain Microvascular Endothelial Cells Tight Junction Proteins and Cell Adhesion Molecules: Transmigration across the in Vitro Blood-Brain Barrier","volume":"385","author":"Verma","year":"2009","journal-title":"Virology"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Hsieh, J.T., and John, A.L.S. (2020). Japanese Encephalitis Virus and Its Mechanisms of Neuroinvasion. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008260"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.neuron.2019.07.015","article-title":"Mechanisms of Pathogen Invasion into the Central Nervous System","volume":"103","author":"Cain","year":"2019","journal-title":"Neuron"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mustaf\u00e1, Y.M., Meuren, L.M., Coelho, S.V.A., and de Arruda, L.B. (2019). Pathways Exploited by Flaviviruses to Counteract the Blood-Brain Barrier and Invade the Central Nervous System. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.00525"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Marshall, E.M., Koopmans, M.P.G., and Rockx, B. (2022). A Journey to the Central Nervous System: Routes of Flaviviral Neuroinvasion in Human Disease. Viruses, 14.","DOI":"10.3390\/v14102096"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.tmaid.2010.06.004","article-title":"Tick-Borne Encephalitis: Pathogenesis and Clinical Implications","volume":"8","author":"Dobler","year":"2010","journal-title":"Travel Med. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ruzek, D., Sal\u00e1t, J., Singh, S.K., and Kopeck\u00fd, J. (2011). Breakdown of the Blood-Brain Barrier during Tick-Borne Encephalitis in Mice Is Not Dependent on CD8+ T-Cells. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020472"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"12202","DOI":"10.1128\/JVI.01215-14","article-title":"Type I Interferon Protects Mice from Fatal Neurotropic Infection with Langat Virus by Systemic and Local Antiviral Responses","volume":"88","author":"Weber","year":"2014","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.virol.2017.04.012","article-title":"Tick-Borne Encephalitis Virus Infects Human Brain Microvascular Endothelial Cells without Compromising Blood-Brain Barrier Integrity","volume":"507","author":"Palus","year":"2017","journal-title":"Virology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1096\/fj.04-3458fje","article-title":"Blood-Brain Barrier-Specific Properties of a Human Adult Brain Endothelial Cell Line","volume":"19","author":"Weksler","year":"2005","journal-title":"FASEB J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1111\/j.1471-4159.2008.05730.x","article-title":"The Human Brain Endothelial Cell Line hCMEC\/D3 as a Human Blood-Brain Barrier Model for Drug Transport Studies","volume":"107","author":"Poller","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/2045-8118-10-33","article-title":"Comparative Study of Four Immortalized Human Brain Capillary Endothelial Cell Lines, hCMEC\/D3, hBMEC, TY10, and BB19, and Optimization of Culture Conditions, for an in Vitro Blood\u2013Brain Barrier Model for Drug Permeability Studies","volume":"10","author":"Eigenmann","year":"2013","journal-title":"Fluids Barriers CNS"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Sade, H., Baumgartner, C., Hugenmatter, A., Moessner, E., Freskg\u00e5rd, P.-O., and Niewoehner, J. (2014). A Human Blood-Brain Barrier Transcytosis Assay Reveals Antibody Transcytosis Influenced by pH-Dependent Receptor Binding. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096340"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/j.bios.2016.06.014","article-title":"Direct Quantification of Transendothelial Electrical Resistance in Organs-on-Chips","volume":"85","author":"Odijk","year":"2016","journal-title":"Biosens. Bioelectron."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Yang, Z., Huang, C., Wu, Y., Chen, B., Zhang, W., and Zhang, J. (2019). Autophagy Protects the Blood-Brain Barrier Through Regulating the Dynamic of Claudin-5 in Short-Term Starvation. Front. Physiol., 10.","DOI":"10.3389\/fphys.2019.00002"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1099\/jgv.0.001416","article-title":"Basic Insights into Zika Virus Infection of Neuroglial and Brain Endothelial Cells","volume":"101","author":"Mutso","year":"2020","journal-title":"J. Gen. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1134\/S0006297909120050","article-title":"C-Terminal Fragment of Human Laminin-Binding Protein Contains a Receptor Domain for Venezuelan Equine Encephalitis and Tick-Borne Encephalitis Viruses","volume":"74","author":"Malygin","year":"2009","journal-title":"Biochem. Mosc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1111\/j.1462-5822.2011.01624.x","article-title":"Vimentin Binding Is Critical for Infection by the Virulent Strain of Japanese Encephalitis Virus","volume":"13","author":"Liang","year":"2011","journal-title":"Cell. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1002\/jcp.1041490118","article-title":"Recycling Kinetics and Transcytosis of Transferrin in Primary Cultures of Bovine Brain Microvessel Endothelial Cells","volume":"149","author":"Raub","year":"1991","journal-title":"J. Cell. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Hasebe, R., Suzuki, T., Makino, Y., Igarashi, M., Yamanouchi, S., Maeda, A., Horiuchi, M., Sawa, H., and Kimura, T. (2010). Transcellular Transport of West Nile Virus-like Particles across Human Endothelial Cells Depends on Residues 156 and 159 of Envelope Protein. BMC Microbiol., 10.","DOI":"10.1186\/1471-2180-10-165"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Papa, M.P., Meuren, L.M., Coelho, S.V.A., de Oliveira Lucas, C.G., Mustaf\u00e1, Y.M., Lemos Matassoli, F., Silveira, P.P., Frost, P.S., Pezzuto, P., and Ribeiro, M.R. (2017). Zika Virus Infects, Activates, and Crosses Brain Microvascular Endothelial Cells, without Barrier Disruption. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.02557"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.virol.2006.09.015","article-title":"Genetic Characterization of Tick-Borne Flaviviruses: New Insights into Evolution, Pathogenetic Determinants and Taxonomy","volume":"361","author":"Grard","year":"2007","journal-title":"Virology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/0042-6822(92)90545-Z","article-title":"Cloning and Sequence Analysis of the Genes Encoding the Nonstructural Proteins of Langat Virus and Comparative Analysis with Other Flaviviruses","volume":"188","author":"Schmaljohn","year":"1992","journal-title":"Virology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1084\/jem.150.2.379","article-title":"Effect of Cytochalasin B on the Maturation of Enveloped Viruses","volume":"150","author":"Griffin","year":"1979","journal-title":"J. Exp. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/0042-6822(86)90090-5","article-title":"Involvement of Actin Filaments in Budding of Measles Virus: Studies on Cytoskeletons of Infected Cells","volume":"149","author":"Bohn","year":"1986","journal-title":"Virology"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Calvert, B.A., Quiroz, E.J., Lorenzana, Z., Doan, N., Kim, S., Senger, C.N., Anders, J.J., Wallace, W.D., Salomon, M.P., and Henley, J. (2023). Neutrophilic Inflammation Promotes SARS-CoV-2 Infectivity and Augments the Inflammatory Responses in Airway Epithelial Cells. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1112870"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s41182-017-0072-7","article-title":"Identification of Novel Antiviral of Fungus-Derived Brefeldin A against Dengue Viruses","volume":"45","author":"Raekiansyah","year":"2017","journal-title":"Trop. Med. Health"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s12250-019-00086-4","article-title":"The Role of Host Cytoskeleton in Flavivirus Infection","volume":"34","author":"Zhang","year":"2019","journal-title":"Virol. Sin."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Farias, K.J.S., Machado, P.R.L., de Almeida J\u00fanior, R.F., and Lopes da Fonseca, B.A. (2019). Brefeldin A and Cytochalasin B Reduce Dengue Virus Replication in Cell Cultures but Do Not Protect Mice against Viral Challenge. Access Microbiol., 1.","DOI":"10.1099\/acmi.0.000041"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Zhou, W., Woodson, M., Neupane, B., Bai, F., Sherman, M.B., Choi, K.H., Neelakanta, G., and Sultana, H. (2018). Exosomes Serve as Novel Modes of Tick-Borne Flavivirus Transmission from Arthropod to Human Cells and Facilitates Dissemination of Viral RNA and Proteins to the Vertebrate Neuronal Cells. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1006764"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.bbrc.2007.03.051","article-title":"Up-Regulated Expression of \u03923 Integrin Induced by Dengue Virus Serotype 2 Infection Associated with Virus Entry into Human Dermal Microvascular Endothelial Cells","volume":"356","author":"Zhang","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1099\/vir.0.052613-0","article-title":"Integrins Modulate the Infection Efficiency of West Nile Virus into Cells","volume":"94","author":"Schmidt","year":"2013","journal-title":"J. Gen. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1002\/jmr.2399","article-title":"Force-Induced Globule\u2013Coil Transition in Laminin Binding Protein and Its Role for Viral\u2013Cell Membrane Fusion","volume":"27","author":"Zaitsev","year":"2014","journal-title":"J. Mol. Recognit."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.stem.2019.11.016","article-title":"Zika Virus Targets Glioblastoma Stem Cells through a SOX2-Integrin Av\u03b25 Axis","volume":"26","author":"Zhu","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/S0934-8840(99)80021-8","article-title":"Human Laminin Binding Protein as a Cell Receptor for the Tick-Borne Encephalitis Virus","volume":"289","author":"Protopopova","year":"1999","journal-title":"Zentralblatt F\u00fcr Bakteriol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.bbrc.2006.10.091","article-title":"Identification of a Surface Protein on Human Brain Microvascular Endothelial Cells as Vimentin Interacting with Escherichia Coli Invasion Protein IbeA","volume":"351","author":"Zou","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Yang, J., Zou, L., Yang, Y., Yuan, J., Hu, Z., Liu, H., Peng, H., Shang, W., Zhang, X., and Zhu, J. (2016). Superficial Vimentin Mediates DENV-2 Infection of Vascular Endothelial Cells. Sci. Rep., 6.","DOI":"10.1038\/srep38372"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Ramos, I., Stamatakis, K., Oeste, C.L., and P\u00e9rez-Sala, D. (2020). Vimentin as a Multifaceted Player and Potential Therapeutic Target in Viral Infections. Int. J. Mol. Sci., 21.","DOI":"10.20944\/preprints202005.0041.v1"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.neuropharm.2016.08.025","article-title":"Targeting Blood-Brain-Barrier Transcytosis\u2014Perspectives for Drug Delivery","volume":"120","author":"Meyer","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Kubinski, M., Beicht, J., Zdora, I., Saletti, G., Kircher, M., Petry-Gusmag, M., Steffen, I., Puff, C., Jung, K., and Baumg\u00e4rtner, W. (2023). Cross-Reactive Antibodies against Langat Virus Protect Mice from Lethal Tick-Borne Encephalitis Virus Infection. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1134371"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Vigh, J.P., Kincses, A., Ozg\u00fcr, B., Walter, F.R., Santa-Maria, A.R., Valkai, S., Vastag, M., Neuhaus, W., Brodin, B., and D\u00e9r, A. (2021). Transendothelial Electrical Resistance Measurement across the Blood\u2013Brain Barrier: A Critical Review of Methods. Micromachines, 12.","DOI":"10.3390\/mi12060685"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1242\/jcs.107.3.367","article-title":"Concentration-Dependent Effects of Cytochalasin D on Tight Junctions and Actin Filaments in MDCK Epithelial Cells","volume":"107","author":"Stevenson","year":"1994","journal-title":"J. Cell Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/S1386-6532(02)00168-3","article-title":"Development of a Quantitative Real-Time RT-PCR Assay with Internal Control for the Laboratory Detection of Tick Borne Encephalitis Virus (TBEV) RNA","volume":"27","author":"Schwaiger","year":"2003","journal-title":"J. Clin. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s12974-016-0487-9","article-title":"Type I Interferon Response in Olfactory Bulb, the Site of Tick-Borne Flavivirus Accumulation, Is Primarily Regulated by IPS-1","volume":"13","author":"Kurhade","year":"2016","journal-title":"J. Neuroinflam."},{"key":"ref_56","first-page":"141","article-title":"Monoclonal Antibodies Directed against Tick-Borne Encephalitis Virus with Neutralizing Activity In Vivo","volume":"38","author":"Niedrig","year":"1994","journal-title":"Acta Virol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/5\/2342\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:48:05Z","timestamp":1760028485000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/5\/2342"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,6]]},"references-count":56,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["ijms26052342"],"URL":"https:\/\/doi.org\/10.3390\/ijms26052342","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,6]]}}}