{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T21:32:43Z","timestamp":1771968763220,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T00:00:00Z","timestamp":1595980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["31003A_163438"],"award-info":[{"award-number":["31003A_163438"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Swiss Food Safety and Veterinary Office","award":["MON-108"],"award-info":[{"award-number":["MON-108"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Tissues from two cows with neurological signs that were admitted to the Vetsuisse Faculty under suspicion of rabies and bovine spongiform encephalopathy (BSE), respectively, were further analyzed for this case report. After histopathological examination and exclusion of BSE and rabies, the animals were diagnosed with etiologically unresolved disseminated non-suppurative encephalitis. Using next-generation sequencing, we detected the full genome of bovine polyomavirus 2 (BoPyV2) in brain samples from both animals. This virus has been identified in beef samples in three independent studies conducted in the United States and Germany, but has not been linked to any disease. Analysis of the two new BoPyV2 genome sequences revealed close phylogenetic relationships to one another and to BoPyV2 isolates detected in beef samples. In situ hybridization demonstrated the presence of viral nucleic acid in all investigated brain areas and in areas with signs of inflammation in both animals. Thus, we provide the first evidence that BoPyV2 is a probable cause of non-suppurative encephalitis in cattle, and encourage further molecular and serological testing to elucidate the disease\u2019s epidemiology, as well as experimental transmission studies to prove causality between the infection and disease.<\/jats:p>","DOI":"10.3390\/pathogens9080620","type":"journal-article","created":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T03:36:38Z","timestamp":1596080198000},"page":"620","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Bovine Polyomavirus 2 is a Probable Cause of Non-Suppurative Encephalitis in Cattle"],"prefix":"10.3390","volume":"9","author":[{"given":"Melanie M.","family":"Hierweger","sequence":"first","affiliation":[{"name":"Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, 3010 Bern, Switzerland"},{"name":"School for Cellular and Biomedical Sciences, University of Bern, 3010 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel C.","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, 3010 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6800-5129","authenticated-orcid":false,"given":"Torsten","family":"Seuberlich","sequence":"additional","affiliation":[{"name":"Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, 3010 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1515\/hsz-2016-0345","article-title":"The biology of JC polyomavirus","volume":"398","author":"Assetta","year":"2017","journal-title":"Biol. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Alcendor, D.J. (2019). BK Polyomavirus Virus Glomerular Tropism: Implications for Virus Reactivation from Latency and Amplification during Immunosuppression. J. Clin. Med., 8.","DOI":"10.3390\/jcm8091477"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/j.1399-3062.2006.00166.x","article-title":"Polyomavirus-associated nephropathy: Update of clinical management in kidney transplant patients","volume":"8","author":"Trofe","year":"2006","journal-title":"Transpl. Infect. Dis. Off. J. Transplant. Soc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1126\/science.1152586","article-title":"Clonal integration of a polyomavirus in human Merkel cell carcinoma","volume":"319","author":"Feng","year":"2008","journal-title":"Science"},{"key":"ref_5","unstructured":"Knipe, D., and Howley, P. (2013). Polyomaviruses. Fields Virology, Lipincott, Williams&Wilkins. [6th ed.]."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S47","DOI":"10.21037\/tlcr.2020.02.03","article-title":"SV40 and human mesothelioma","volume":"9","author":"Carbone","year":"2020","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1177\/1947601910395580","article-title":"Tissue Tropism of SV40 Transformation of Human Cells: Role of the Viral Regulatory Region and of Cellular Oncogenes","volume":"1","author":"Zhang","year":"2010","journal-title":"Genes Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1128\/jvi.55.3.823-825.1985","article-title":"Decreasing the number of 68-base-pair tandem repeats in the BK virus transcriptional control region reduces plaque size and enhances transforming capacity","volume":"55","author":"Watanabe","year":"1985","journal-title":"J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/path.5127","article-title":"The two-faced nature of BK polyomavirus: Lytic infection or non-lytic large-T-positive carcinoma","volume":"246","author":"Nickeleit","year":"2018","journal-title":"J. Pathol."},{"key":"ref_10","unstructured":"(2019, November 13). ICTVonline. Available online: https:\/\/talk.ictvonline.org\/\/taxonomy\/p\/taxonomy-history?taxnode_id=201851632."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Schowalter, R.M., and Buck, C.B. (2013). The Merkel cell polyomavirus minor capsid protein. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003558"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3201\/eid1901.121078","article-title":"Novel polyomavirus associated with brain tumors in free-ranging raccoons, western United States","volume":"19","author":"Giannitti","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.virol.2014.08.025","article-title":"What is for dinner? Viral metagenomics of US store bought beef, pork, and chicken","volume":"468\u2013470","author":"Zhang","year":"2014","journal-title":"Virology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1128\/iai.14.1.225-231.1976","article-title":"Identification of the stumptailed macaque virus as a new papovavirus","volume":"14","author":"Reissig","year":"1976","journal-title":"Infect. Immun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/BF01314984","article-title":"A possible bovine polyomavirus","volume":"66","author":"Coackley","year":"1980","journal-title":"Arch. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/0378-1135(87)90142-8","article-title":"The isolation of a virus resembling a polyomavirus from normal calves","volume":"15","author":"Westcott","year":"1987","journal-title":"Vet. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1099\/0022-1317-72-11-2739","article-title":"Frequent detection of bovine polyomavirus in commercial batches of calf serum by using the polymerase chain reaction","volume":"72","author":"Schuurman","year":"1991","journal-title":"J. Gen. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7886","DOI":"10.1128\/AEM.01090-06","article-title":"Identification of human and animal adenoviruses and polyomaviruses for determination of sources of fecal contamination in the environment","volume":"72","author":"Hundesa","year":"2006","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.watres.2014.04.013","article-title":"Application of human and animal viral microbial source tracking tools in fresh and marine waters from five different geographical areas","volume":"59","author":"Rusinol","year":"2014","journal-title":"Water Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1080\/00480169.2005.36465","article-title":"Detection and molecular characterisation of bovine polyomavirus in bovine sera in New Zealand","volume":"53","author":"Wang","year":"2005","journal-title":"N. Z. Vet. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/BF01315306","article-title":"Human exposure to bovine polyomavirus: A zoonosis?","volume":"87","author":"Parry","year":"1986","journal-title":"Arch. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1099\/vir.0.000033","article-title":"Hamburger polyomaviruses","volume":"96","author":"Peretti","year":"2015","journal-title":"J. Gen. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.ijfoodmicro.2016.10.024","article-title":"Detection and genome characterization of bovine polyomaviruses in beef muscle and ground beef samples from Germany","volume":"241","author":"Grafe","year":"2017","journal-title":"Int. J. food Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.virol.2016.03.009","article-title":"Exploring the virome of cattle with non-suppurative encephalitis of unknown etiology by metagenomics","volume":"493","author":"Wuthrich","year":"2016","journal-title":"Virology"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Hierweger, M.M., Werder, S., and Seuberlich, T. (2020). Parainfluenza Virus 5 Infection in Neurological Disease and Encephalitis of Cattle. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020498"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8125","DOI":"10.1093\/nar\/15.20.8125","article-title":"An analysis of 5\u2019-noncoding sequences from 699 vertebrate messenger RNAs","volume":"15","author":"Kozak","year":"1987","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3979","DOI":"10.1128\/jvi.66.7.3979-3985.1992","article-title":"Common and unique features of T antigens encoded by the polyomavirus group","volume":"66","author":"Pipas","year":"1992","journal-title":"J. Virol."},{"key":"ref_28","unstructured":"Vandevelde, M., Higgins, R.J., and Oevermann, A. (2012). Veterinary Neuropathology: Essentials of Theory and Practice, Wiley-Blackwell. [1st ed.]."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nrmicro2949","article-title":"The changing face of pathogen discovery and surveillance","volume":"11","author":"Lipkin","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbi.2016.03.010","article-title":"The blood-brain barrier in systemic inflammation","volume":"60","author":"Varatharaj","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jcv.2008.04.011","article-title":"Detection of polyomavirus SV40 in tonsils from immunocompetent children","volume":"43","author":"Patel","year":"2008","journal-title":"J. Clin. Virol. Off. Publ. Pan Am. Soc. Clin. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1002\/jmv.21786","article-title":"JCV\/BKV and SV40 viral load in lymphoid tissues of young immunocompetent children from an area of north-east Italy","volume":"82","author":"Comar","year":"2010","journal-title":"J. Med Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1038\/jid.2009.392","article-title":"Inflammatory monocytes are a reservoir for Merkel cell polyomavirus","volume":"130","author":"Mertz","year":"2010","journal-title":"J. Invest. Derm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0733-8619(18)31105-8","article-title":"Progressive multifocal leukoencephalopathy","volume":"2","author":"Brooks","year":"1984","journal-title":"Neurologic Clinics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/S1474-4422(10)70040-5","article-title":"Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: Clinical features and pathogenesis","volume":"9","author":"Tan","year":"2010","journal-title":"Lancet. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1002\/ana.21619","article-title":"Fulminant JC virus encephalopathy with productive infection of cortical pyramidal neurons","volume":"65","author":"Wuthrich","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Antoniolli, L., Borges, R., and Goldani, L.Z. (2017). BK Virus Encephalitis in HIV-Infected Patients: Case Report and Review. Case Rep. Med., 2017.","DOI":"10.1155\/2017\/4307468"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1093\/jnen\/63.7.750","article-title":"Meningoencephalitis and demyelination are pathologic manifestations of primary polyomavirus infection in immunosuppressed rhesus monkeys","volume":"63","author":"Axthelm","year":"2004","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1097\/NEN.0b013e318180f0d5","article-title":"Productive simian virus 40 infection of neurons in immunosuppressed Rhesus monkeys","volume":"67","author":"Dang","year":"2008","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Limam, S., Missaoui, N., Bdioui, A., Yacoubi, M.T., Krifa, H., Mokni, M., and Selmi, B. (2020). Investigation of simian virus 40 (SV40) and human JC, BK, MC, KI, and WU polyomaviruses in glioma. J. Neurovirol.","DOI":"10.1007\/s13365-020-00833-4"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.14202\/vetworld.2017.1367-1377","article-title":"Metabolic and immunological changes in transition dairy cows: A review","volume":"10","author":"Wankhade","year":"2017","journal-title":"Vet. World"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.tvjl.2013.07.024","article-title":"Bovine viral diarrhoea: Pathogenesis and diagnosis","volume":"199","author":"Lanyon","year":"2014","journal-title":"Vet. J."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/9\/8\/620\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:52:37Z","timestamp":1760176357000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/9\/8\/620"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,29]]},"references-count":42,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["pathogens9080620"],"URL":"https:\/\/doi.org\/10.3390\/pathogens9080620","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,29]]}}}