{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:57:14Z","timestamp":1792684634016,"version":"4.5.0"},"reference-count":50,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T00:00:00Z","timestamp":1695945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Veterinary Medicine Vienna"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>As evidenced by sero-epidemiological studies, infections of horses with the tick-borne encephalitis virus (TBEV) occur frequently in TBEV-endemic areas. However, there are only very few reports of clinical cases. A possible underreporting may be due to a variety of diagnostic challenges. In this study, ELISA and neutralization tests were applied to serum samples. Brain tissue samples were investigated for the presence of nucleic acids of TBEV, Equid alphaherpesvirus\u00a01, Borna disease virus 1, West Nile and Usutu viruses, rustrela virus, as well as Eastern, Western, and Venezuelan equine encephalitis viruses with RT-qPCR, RT-PCR, and qPCR, respectively. TBEV-specific amplification products were subjected to Sanger sequencing. In addition, a direct fluorescent antibody test for rabies was performed. Clinical and patho-histological findings are reported. Using specific RT-qPCR and RT-PCR assays, TBEV nucleic acids were demonstrated in brain tissue samples. Sequencing revealed the Western (formerly Central) European subtype of TBEV as the etiological agent. A high titer of TBEV-specific neutralizing antibodies was found in the serum. RNAscope in situ hybridization revealed TBEV RNA confined to neuronal cell bodies and processes. No other pathogens or nucleic acids thereof could be detected. Diagnostic procedures need to be carried out early after the onset of neurological signs to allow for a final etiological diagnosis of acute TBEV infections in horses.<\/jats:p>","DOI":"10.3390\/v15102022","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T02:47:30Z","timestamp":1695955650000},"page":"2022","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Severe Neurologic Disease in a Horse Caused by Tick-Borne Encephalitis Virus, Austria, 2021"],"prefix":"10.3390","volume":"15","author":[{"given":"Phebe","family":"de Heus","sequence":"first","affiliation":[{"name":"Clinical Unit of Equine Internal Medicine, University of Veterinary Medicine Vienna, Veterin\u00e4rplatz 1, 1210 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5897-5263","authenticated-orcid":false,"given":"Zolt\u00e1n","family":"Bag\u00f3","sequence":"additional","affiliation":[{"name":"Institute for Veterinary Disease Control M\u00f6dling, Austrian Agency for Health and Food Safety Ltd. (AGES), Robert Koch-Gasse 17, 2340 M\u00f6dling, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4028-4151","authenticated-orcid":false,"given":"Pia","family":"Weidinger","sequence":"additional","affiliation":[{"name":"Viral Zoonoses, Emerging and Vector-Borne Infections Group, Institute of Virology, University of Veterinary Medicine Vienna, Veterin\u00e4rplatz 1, 1210 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilara","family":"Lale","sequence":"additional","affiliation":[{"name":"Clinical Unit of Equine Internal Medicine, University of Veterinary Medicine Vienna, Veterin\u00e4rplatz 1, 1210 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5103-8402","authenticated-orcid":false,"given":"Dagmar S.","family":"Trachsel","sequence":"additional","affiliation":[{"name":"Clinical Unit of Equine Internal Medicine, University of Veterinary Medicine Vienna, Veterin\u00e4rplatz 1, 1210 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Revilla-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Institute for Veterinary Disease Control M\u00f6dling, Austrian Agency for Health and Food Safety Ltd. (AGES), Robert Koch-Gasse 17, 2340 M\u00f6dling, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaspar","family":"Matiasek","sequence":"additional","affiliation":[{"name":"Section of Clinical & Comparative Neuropathology, Institute of Veterinary Pathology, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Feodor-Lynen Stra\u00dfe 23, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3548-571X","authenticated-orcid":false,"given":"Norbert","family":"Nowotny","sequence":"additional","affiliation":[{"name":"Viral Zoonoses, Emerging and Vector-Borne Infections Group, Institute of Virology, University of Veterinary Medicine Vienna, Veterin\u00e4rplatz 1, 1210 Vienna, Austria"},{"name":"Department of Basic Medical Sciences, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Healthcare City, Building 14, Dubai P.O. Box 505055, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/B978-0-12-800172-1.00005-7","article-title":"Chapter 5: Arboviruses Pathogenic for Domestic and Wild Animals","volume":"Volume 89","author":"Rudolf","year":"2014","journal-title":"Advances in Virus Research"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e2470","DOI":"10.1002\/rmv.2470","article-title":"Tick-borne Encephalitis: A Comprehensive Review of the Epidemiology, Virology, and Clinical Picture","volume":"33","author":"Chiffi","year":"2023","journal-title":"Rev. Med. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/S1438-4221(02)80014-5","article-title":"Tick-Borne Encephalitis (TBE) in Dogs","volume":"291","author":"Leschnik","year":"2002","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s004010050811","article-title":"Tick-Borne Encephalitis in Dogs: Neuropathological Findings and Distribution of Antigen","volume":"95","author":"Suchy","year":"1998","journal-title":"Acta Neuropathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"226","DOI":"10.4149\/av_2020_212","article-title":"Tick-Borne Encephalitis in Domestic Animals","volume":"64","author":"Salat","year":"2020","journal-title":"Acta Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"635","DOI":"10.3201\/eid1904.121450","article-title":"Tick-Borne Encephalitis Virus in Horses, Austria, 2011","volume":"19","author":"Rushton","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"de Heus, P., Kolodziejek, J., Hub\u00e1lek, Z., Dimmel, K., Racher, V., Nowotny, N., and Cavalleri, J.M.V. (2021). West Nile Virus and Tick-Borne Encephalitis Virus Are Endemic in Equids in Eastern Austria. Viruses, 13.","DOI":"10.3390\/v13091873"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.3201\/eid1510.090743","article-title":"Tick-Borne Encephalitis from Eating Goat Cheese in a Mountain Region of Austria","volume":"15","author":"Holzmann","year":"2009","journal-title":"Emerg. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1136\/vr.150.7.218","article-title":"Tickborne Encephalitis in a Mouflon (Ovis Ammon Musimon)","volume":"150","author":"Bauder","year":"2002","journal-title":"Vet. Rec."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"102028","DOI":"10.1016\/j.ttbdis.2022.102028","article-title":"Systematic Review on the Non-Vectorial Transmission of Tick-Borne Encephalitis Virus (TBEv)","volume":"13","author":"Martello","year":"2022","journal-title":"Ticks Tick Borne Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.ttbdis.2010.10.007","article-title":"Tick-Borne Encephalitis 2010: Epidemiology, Risk Areas, and Virus Strains in Europe and Asia-An Overview","volume":"2","year":"2011","journal-title":"Ticks Tick Borne Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1017\/S0031182099006083","article-title":"Seasonal Synchrony: The Key to Tick-Borne Encephalitis Foci Identified by Satellite Data","volume":"121","author":"Randolph","year":"2000","journal-title":"Parasitology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"101972","DOI":"10.1016\/j.ttbdis.2022.101972","article-title":"The Epidemiology of Infectious Diseases in Europe in 2020 versus 2017\u20132019 and the Rise of Tick-Borne Encephalitis (1995\u20132020)","volume":"13","author":"Jenkins","year":"2022","journal-title":"Ticks Tick Borne Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1159\/000324023","article-title":"Experimental Infection of Goats with Tick-Borne Encephalitis Virus and Possibilities to Prevent Virus Transmission by Raw Goat Milk","volume":"55","author":"Balogh","year":"2012","journal-title":"Intervirology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"105511","DOI":"10.1016\/j.antiviral.2022.105511","article-title":"Functional Characterization and Immunogenicity of a Novel Vaccine Candidate against Tick-Borne Encephalitis Virus Based on Leishmania-Derived Virus-like Particles","volume":"209","author":"Zimna","year":"2023","journal-title":"Antivir. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7257","DOI":"10.1016\/j.vaccine.2018.10.034","article-title":"Development and Testing of a New Tick-Borne Encephalitis Virus Vaccine Candidate for Veterinary Use","volume":"36","author":"Eyer","year":"2018","journal-title":"Vaccine"},{"key":"ref_17","first-page":"227","article-title":"Zeckenenzephalitis Beim Pferd","volume":"123","author":"Waldvogel","year":"1981","journal-title":"Schweiz. Arch. Tierheilkd."},{"key":"ref_18","first-page":"235","article-title":"Fr\u00fchsommermeningoenzephalitis- (FSME-)Infektion in Einer \u00d6sterreichischen Pferdepopulation","volume":"27","author":"Luckschander","year":"1999","journal-title":"Tierarztl. Prax."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Conze, T.M., Bag\u00f3, Z., Revilla-Fern\u00e1ndez, S., Schlegel, J., Goehring, L.S., and Matiasek, K. (2021). Tick-Borne Encephalitis Virus (Tbev) Infection in Two Horses. Viruses, 13.","DOI":"10.3390\/v13091775"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Fouch\u00e9, N., Oesch, S., Ziegler, U., and Gerber, V. (2021). Clinical Presentation and Laboratory Diagnostic Work-up of a Horse with Tick-Borne Encephalitis in Switzerland. Viruses, 13.","DOI":"10.3390\/v13081474"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1111\/jvim.16533","article-title":"Neurological Disease Suspected to Be Caused by Tick-Borne Encephalitis Virus Infection in 6 Horses in Switzerland","volume":"36","author":"Magouras","year":"2022","journal-title":"J. Vet. Intern. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"102220","DOI":"10.1016\/j.ttbdis.2023.102220","article-title":"Seroprevalence of Tick-Borne Encephalitis Virus in Wild and Domestic Animals in Northern Germany","volume":"14","author":"Topp","year":"2023","journal-title":"Ticks Tick Borne Dis."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Pautienius, A., Armonaite, A., Simkute, E., Zagrabskaite, R., Buitkuviene, J., Alpizar-Jara, R., Grigas, J., Zakiene, I., Zienius, D., and Salomskas, A. (2021). Cross-Sectional Study on the Prevalence and Factors Influencing Occurrence of Tick-Borne Encephalitis in Horses in Lithuania. Pathogens, 10.","DOI":"10.3390\/pathogens10020140"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Napp, S., Llorente, F., Beck, C., Jose-cunilleras, E., Soler, M., Pailler-garc\u00eda, L., Amaral, R., Aguilera-sep\u00falveda, P., Pifarr\u00e9, M., and Molina-l\u00f3pez, R. (2021). Widespread Circulation of Flaviviruses in Horses and Birds in Northeastern Spain (Catalonia) between 2010 and 2019. Viruses, 13.","DOI":"10.3390\/v13122404"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Beck, C., Despr\u00e8s, P., Paulous, S., Vanhomwegen, J., Lowenski, S., Nowotny, N., Durand, B., Garnier, A., Blaise-Boisseau, S., and Guitton, E. (2015). A High-Performance Multiplex Immunoassay for Serodiagnosis of Flavivirus-Associated Neurological Diseases in Horses. BioMed Res. Int., 2015.","DOI":"10.1155\/2015\/678084"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6049","DOI":"10.3390\/ijerph10116049","article-title":"Flaviviruses in Europe: Complex Circulation Patterns and Their Consequences for the Diagnosis and Control of West Nile Disease","volume":"10","author":"Beck","year":"2013","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1111\/tbed.12569","article-title":"A Serological Protein Microarray for Detection of Multiple Cross-Reactive Flavivirus Infections in Horses for Veterinary and Public Health Surveillance","volume":"64","author":"Cleton","year":"2017","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1111\/jvim.16581","article-title":"European College of Equine Internal Medicine Consensus Statement on Equine Flaviviridae Infections in Europe","volume":"36","author":"Cavalleri","year":"2022","journal-title":"J. Vet. Intern. Med."},{"key":"ref_29","unstructured":"World Organisation for Animal Health (WOAH) (2022). Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2022, World Organisation for Animal Health."},{"key":"ref_30","first-page":"e52","article-title":"Infections of Horses and Shrews with Bornaviruses in Upper Austria: A Novel Endemic Area of Borna Disease","volume":"6","author":"Kolodziejek","year":"2017","journal-title":"Emerg. Microbes Infect."},{"key":"ref_31","unstructured":"World Organisation for Animal Health (WOAH) (2022). Manual of Diagnostic Tests and Vaccines for Terrestrial Animals, World Organisation for Animal Health."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kolodziejek, J., Marinov, M., Kiss, B.J., Alexe, V., and Nowotny, N. (2014). The Complete Sequence of a West Nile Virus Lineage 2 Strain Detected in a Hyalomma Marginatum Marginatum Tick Collected from a Song Thrush (Turdus Philomelos) in Eastern Romania in 2013 Revealed Closest Genetic Relationship to Strain Volgograd 2007. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0109905"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.mcp.2006.08.001","article-title":"Reverse Transcription Real-Time PCR Assays for Detection and Quantification of Borna Disease Virus in Diseased Hosts","volume":"21","author":"Schindler","year":"2007","journal-title":"Mol. Cell Probes"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Vina-Rodriguez, A., Eiden, M., Keller, M., Hinrichs, W., and Groschup, M.H. (2016). A Quantitative Real-Time RT-PCR Assay for the Detection of Venezuelan Equine Encephalitis Virus Utilizing a Universal Alphavirus Control RNA. BioMed Res. Int., 2016.","DOI":"10.1155\/2016\/8543204"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1128\/JCM.41.1.379-385.2003","article-title":"Detection of North American Eastern and Western Equine Encephalitis Viruses by Nucleic Acid Amplification Assays","volume":"41","author":"Lambert","year":"2003","journal-title":"J. Clin. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1128\/JCM.39.5.1922-1927.2001","article-title":"Comparison of Flavivirus Universal Primer Pairs and Development of a Rapid, Highly Sensitive Heminested Reverse Transcription-PCR Assay for Detection of Flaviviruses Targeted to a Conserved Region of the NS5 Gene Sequences","volume":"39","author":"Scaramozzino","year":"2001","journal-title":"J. Clin. Microbiol."},{"key":"ref_37","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. Off. Publ. Pan Am. Soc. Clin. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1136\/vr.162.21.688","article-title":"Detection of EHV-1 Neuropathogenic Strains Using Real-Time PCR in the Neural Tissue of Horses with Myeloencephalopathy","volume":"162","author":"Leutenegger","year":"2008","journal-title":"Vet. Rec."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"274","DOI":"10.3201\/eid1902.121191","article-title":"Usutu Virus, Italy, 1996","volume":"19","author":"Bakonyi","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1038\/s41467-023-36204-w","article-title":"Mystery of Fatal \u2018Staggering Disease\u2019 Unravelled: Novel Rustrela Virus Causes Severe Meningoencephalomyelitis in Domestic Cats","volume":"14","author":"Matiasek","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_41","first-page":"227","article-title":"The Method of \u00b4right and Wrong Cases\u00b4 (\u00b4constant Stimuli\u00b4) without Gauss\u2019s Formulae","volume":"2","author":"Spearman","year":"1908","journal-title":"Br. J. Psychol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1007\/BF01863914","article-title":"Beitrag Zur Kollektiven Behandlung Pharmakologischer Reihenversuche","volume":"162","year":"1931","journal-title":"Arch. Exp. Pathol. Pharmakol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Gothe, L.M.R., Ganzenberg, S., Ziegler, U., Obiegala, A., Lohmann, K.L., Sieg, M., Vahlenkamp, T.W., Groschup, M.H., H\u00f6r\u00fcgel, U., and Pfeffer, M. (2023). Horses as Sentinels for the Circulation of Flaviviruses in Eastern\u2013Central Germany. Viruses, 15.","DOI":"10.3390\/v15051108"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.vetmic.2012.12.041","article-title":"Tick-Borne Encephalitis Virus (TBEV) Infection in Horses: Clinical and Laboratory Findings and Epidemiological Investigations","volume":"163","author":"Klaus","year":"2013","journal-title":"Vet. Microbiol."},{"key":"ref_45","first-page":"312","article-title":"Die \u00c4tiologie Der Lipizzanerseuche in Piber 1983: Equines Herpesvirus 1","volume":"71","author":"Nowotny","year":"1984","journal-title":"Wien Tierarztl Monatsschr"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1136\/vr.143.1.21","article-title":"Borna Disease in Austrian Horses","volume":"143","author":"Suchy","year":"1998","journal-title":"Vet. Rec."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5655","DOI":"10.1128\/JVI.74.12.5655-5658.2000","article-title":"Isolation and Characterization of a New Subtype of Borna Disease Virus","volume":"74","author":"Nowotny","year":"2000","journal-title":"J. Virol."},{"key":"ref_48","first-page":"1189","article-title":"Emergence of West Nile Virus Lineage 2 in Europe: Characteristics of the First Seven Cases of West Nile Neuroinvasive Disease in Horses in Austria","volume":"67","author":"Kolodziejek","year":"2019","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/s41586-020-2812-9","article-title":"Relatives of Rubella Virus in Diverse Mammals","volume":"586","author":"Bennett","year":"2020","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Weiss, V., Weidinger, P., Matt, J., Weissenbacher-Lang, C., Nowotny, N., and Weissenb\u00f6ck, H. (2023). Rustrela Virus-Associated Encephalomyelitis (\u2018Staggering Disease\u2019) in Cats from Eastern Austria, 1994\u20132016. Viruses, 15.","DOI":"10.3390\/v15081621"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/10\/2022\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:01:33Z","timestamp":1760130093000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/10\/2022"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,29]]},"references-count":50,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["v15102022"],"URL":"https:\/\/doi.org\/10.3390\/v15102022","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,29]]}}}