{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T10:16:39Z","timestamp":1789121799301,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013400","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000}}],"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["504757758"],"award-info":[{"award-number":["504757758"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Borna disease virus 1 (BoDV-1) has long been recognized as a cause of fatal encephalitis in animals and was only recently identified as a zoonotic pathogen causing a similar disease in humans. This study provides the first comprehensive comparative analysis of BoDV-1-induced neuropathology in human and animal end hosts, including horses, sheep, and alpacas. Using immunohistochemical analyses, we investigated the topographical distribution of BoDV-1 and inflammatory responses in the central nervous system across 19 cases. Key findings reveal distinct differences and overlaps between humans and animals. While humans exhibited heterogeneous patterns especially of the lymphocyte infiltration, animals displayed more species-specific inflammation and viral spread patterns. In horses, the hippocampus and basal ganglia were consistently affected, whereas sheep showed predominant involvement of the frontal cortex and stria olfactoria. Alpacas demonstrated a less uniform distribution but highlighted the brainstem and basal ganglia as critical sites. Intriguingly, across all species, a negative association was observed between lymphocyte infiltration and the number of BoDV-1-infected cells. These findings enhance our understanding of BoDV-1 pathogenesis and is a first step of cross-species comparison in unraveling disease mechanisms in BoDV-1 infection. Further research is warranted to elucidate the implications of these findings for therapeutic strategies and to explore the entry and dissemination routes of BoDV-1 in different hosts.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013400","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T17:39:57Z","timestamp":1754329197000},"page":"e1013400","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mapping Bornavirus encephalitis\u2014A comparative study of viral spread and immune response in human and animal dead-end hosts"],"prefix":"10.1371","volume":"21","author":[{"given":"Yannik","family":"Vollmuth","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Jungb\u00e4ck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Przemyslaw","family":"Grochowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"M\u00f6gele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonhard","family":"Stark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niku S.","family":"Zarrabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Schlegel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Schaller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"M\u00e4rkl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaspar","family":"Matiasek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1948-1580","authenticated-orcid":true,"given":"Friederike","family":"Liesche-Starnecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,8,4]]},"reference":[{"issue":"3","key":"ppat.1013400.ref001","first-page":"147","article-title":"Borna disease virus (BDV), a (zoonotic?) worldwide pathogen. A review of the history of the disease and the virus infection with comprehensive bibliography","volume":"44","author":"R D\u00fcrrwald","year":"1997","journal-title":"Zentralbl Veterinarmed B"},{"issue":"14","key":"ppat.1013400.ref002","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1056\/NEJMc1803115","article-title":"Fatal Encephalitic Borna Disease Virus 1 in Solid-Organ Transplant Recipients","volume":"379","author":"K Schlottau","year":"2018","journal-title":"N Engl J Med"},{"key":"ppat.1013400.ref003","first-page":"434","article-title":"Selten, aber t\u00f6dlich: Bornavirus-Enzephalitis","volume":"77","author":"M B\u00f6hmer","year":"2022","journal-title":"Bayrisches \u00c4rzteblatt"},{"issue":"4","key":"ppat.1013400.ref004","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/S1473-3099(19)30546-8","article-title":"Zoonotic spillover infections with Borna disease virus 1 leading to fatal human encephalitis, 1999-2019: an epidemiological investigation","volume":"20","author":"HH Niller","year":"2020","journal-title":"Lancet Infect Dis"},{"issue":"4","key":"ppat.1013400.ref005","doi-asserted-by":"crossref","first-page":"675","DOI":"10.3201\/eid1204.051418","article-title":"Shrews as reservoir hosts of borna disease virus","volume":"12","author":"M Hilbe","year":"2006","journal-title":"Emerg Infect Dis"},{"issue":"12","key":"ppat.1013400.ref006","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.3201\/eid1912.131076","article-title":"Bicolored white-toothed shrews as reservoir for borna disease virus, Bavaria, Germany","volume":"19","author":"M Bourg","year":"2013","journal-title":"Emerg Infect Dis"},{"issue":"4","key":"ppat.1013400.ref007","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0093659","article-title":"The bicolored white-toothed shrew Crocidura leucodon (HERMANN 1780) is an indigenous host of mammalian Borna disease virus","volume":"9","author":"R D\u00fcrrwald","year":"2014","journal-title":"PLoS One"},{"issue":"8","key":"ppat.1013400.ref008","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0137018","article-title":"Shedding of Infectious Borna Disease Virus-1 in Living Bicolored White-Toothed Shrews","volume":"10","author":"D Nobach","year":"2015","journal-title":"PLoS One"},{"issue":"2","key":"ppat.1013400.ref009","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/BF00189527","article-title":"Axonal transport of Borna disease virus along olfactory pathways in spontaneously and experimentally infected rats","volume":"177","author":"JA Morales","year":"1988","journal-title":"Med Microbiol Immunol"},{"issue":"124","key":"ppat.1013400.ref010","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/j.1600-0463.2008.000m8.x","article-title":"Natural and experimental Borna disease virus infections--neuropathology and pathogenetic considerations","author":"G Gosztonyi","year":"2008","journal-title":"APMIS Suppl"},{"issue":"6","key":"ppat.1013400.ref011","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20061318","article-title":"Intranasal Borna Disease Virus (BoDV-1) Infection: Insights into Initial Steps and Potential Contagiosity","volume":"20","author":"A Kupke","year":"2019","journal-title":"Int J Mol Sci"},{"key":"ppat.1013400.ref012","first-page":"1","article-title":"First detected geographical cluster of BoDV-1 encephalitis from same small village in two children: therapeutic considerations and epidemiological implications","author":"L Grosse","year":"2023","journal-title":"Infection"},{"issue":"4","key":"ppat.1013400.ref013","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/s00401-019-02047-3","article-title":"The neuropathology of fatal encephalomyelitis in human Borna virus infection","volume":"138","author":"F Liesche","year":"2019","journal-title":"Acta Neuropathol"},{"key":"ppat.1013400.ref014","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.antiviral.2017.04.018","article-title":"Antiviral activity of favipiravir (T-705) against mammalian and avian bornaviruses","volume":"143","author":"T Tokunaga","year":"2017","journal-title":"Antiviral Res"},{"issue":"10","key":"ppat.1013400.ref015","doi-asserted-by":"crossref","first-page":"3581","DOI":"10.4049\/jimmunol.147.10.3581","article-title":"Transforming growth factor-beta modulates T cell-mediated encephalitis caused by Borna disease virus. Pathogenic importance of CD8 cells and suppression of antibody formation","volume":"147","author":"L Stitz","year":"1991","journal-title":"J Immunol"},{"issue":"17","key":"ppat.1013400.ref016","doi-asserted-by":"crossref","first-page":"9769","DOI":"10.1073\/pnas.96.17.9769","article-title":"T cell ignorance in mice to Borna disease virus can be overcome by peripheral expression of the viral nucleoprotein","volume":"96","author":"J Hausmann","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"ppat.1013400.ref017","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1002393","article-title":"Neurons are MHC class I-dependent targets for CD8 T cells upon neurotropic viral infection","volume":"7","author":"G Chevalier","year":"2011","journal-title":"PLoS Pathog"},{"key":"ppat.1013400.ref018","first-page":"1","article-title":"Detection of bornavirus-reactive antibodies and BoDV-1 RNA only in encephalitis patients from virus endemic areas: a comparative serological and molecular sensitivity, specificity, predictive value, and disease duration correlation study","author":"P Allartz","year":"2023","journal-title":"Infection"},{"key":"ppat.1013400.ref019","doi-asserted-by":"crossref","DOI":"10.2741\/A793","article-title":"The immunopathogenesis of Borna disease virus infection","volume":"7","author":"L Stitz","year":"2002","journal-title":"Front Biosci"},{"key":"ppat.1013400.ref020","doi-asserted-by":"crossref","first-page":"2350168","DOI":"10.1080\/22221751.2024.2350168","article-title":"Comparative study of virus and lymphocyte distribution with clinical data suggests early high dose immunosuppression as potential key factor for the therapy of patients with BoDV-1 infection","author":"Y Vollmuth","year":"2024","journal-title":"Emerg Microbes Infect"},{"issue":"1","key":"ppat.1013400.ref021","first-page":"68","article-title":"Symptomatology and diagnosis of Borna encephalitis of horses. A case analysis of the last 13 years","volume":"19","author":"A Grabner","year":"1991","journal-title":"Tierarztl Prax"},{"issue":"3","key":"ppat.1013400.ref022","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/S0749-0739(17)30097-4","article-title":"Borna disease in horses","volume":"16","author":"JA Richt","year":"2000","journal-title":"Vet Clin North Am Equine Pract"},{"issue":"3","key":"ppat.1013400.ref023","first-page":"213","article-title":"Borna disease of horses. An immunohistological and virological study of naturally infected animals","volume":"64","author":"G Gosztonyi","year":"1984","journal-title":"Acta Neuropathol"},{"key":"ppat.1013400.ref024","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0165-2427(97)00128-1","article-title":"Spontaneous Borna disease in sheep and horses: immunophenotyping of inflammatory cells and detection of MHC-I and MHC-II antigen expression in Borna encephalitis lesions","volume":"61","author":"P Caplazi","year":"1998","journal-title":"Vet Immunol Immunopathol"},{"key":"ppat.1013400.ref025","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/BF02865106","article-title":"Die Ausbreitung der enzephalitischen Reaktion bei der Bornaschen Krankheit der Pferde und deren Beziehung zu der Enzephalitis epidemica, der Heine-Medinschen Krankheit und der Lyssa des Menschen. Eine vergleichend-pathologische Studie","volume":"124","author":"O Seifried","year":"1930","journal-title":"Z ges Neurol Psychiat"},{"issue":"3","key":"ppat.1013400.ref026","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1111\/j.1750-3639.1995.tb00598.x","article-title":"Presence of CD4+ and CD8+ T cells and expression of MHC class I and MHC class II antigen in horses with Borna disease virus-induced encephalitis","volume":"5","author":"T Bilzer","year":"1995","journal-title":"Brain Pathol"},{"issue":"4","key":"ppat.1013400.ref027","doi-asserted-by":"crossref","DOI":"10.1016\/S1473-3099(24)00675-3","article-title":"Neuropathology, pathomechanism, and transmission in zoonotic Borna disease virus 1 infection: a systematic review","volume":"25","author":"N Jungb\u00e4ck","year":"2025","journal-title":"Lancet Infect Dis"},{"issue":"1","key":"ppat.1013400.ref028","doi-asserted-by":"crossref","first-page":"2350168","DOI":"10.1080\/22221751.2024.2350168","article-title":"Comparative study of virus and lymphocyte distribution with clinical data suggests early high dose immunosuppression as potential key factor for the therapy of patients with BoDV-1 infection","volume":"13","author":"Y Vollmuth","year":"2024","journal-title":"Emerg Microbes Infect"},{"issue":"4","key":"ppat.1013400.ref029","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1002\/ana.25873","article-title":"Bornavirus Encephalitis Shows a Characteristic Magnetic Resonance Phenotype in Humans","volume":"88","author":"T Finck","year":"2020","journal-title":"Ann Neurol"},{"key":"ppat.1013400.ref030","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1099\/0022-1317-67-2-235","article-title":"Purification and properties of an intranuclear virus-specific antigen from tissue infected with Borna disease virus","author":"B Haas","year":"1986","journal-title":"J Gen Virol"},{"issue":"5","key":"ppat.1013400.ref031","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1111\/j.1365-2990.2005.00668.x","article-title":"Expression of allograft inflammatory factor-1 and haeme oxygenase-1 in brains of rats infected with the neurotropic Borna disease virus","volume":"31","author":"C Herden","year":"2005","journal-title":"Neuropathol Appl Neurobiol"},{"issue":"6","key":"ppat.1013400.ref032","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1111\/j.1365-2990.2008.00940.x","article-title":"Restricted expression of Borna disease virus glycoprotein in brains of experimentally infected Lewis rats","volume":"34","author":"N Werner-Keiss","year":"2008","journal-title":"Neuropathol Appl Neurobiol"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1013400","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1013400","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T17:48:48Z","timestamp":1754934528000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1013400"}},"subtitle":[],"editor":[{"given":"Andrea","family":"Marzi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,8,4]]},"references-count":32,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1013400","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.ppat.1013400","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,4]]}}}