{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T02:35:09Z","timestamp":1790217309258,"version":"4.1.0"},"reference-count":32,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T00:00:00Z","timestamp":1627257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["398066876\/GRK 2485\/1"],"award-info":[{"award-number":["398066876\/GRK 2485\/1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Since its first discovery by Arnold Theiler in 1918, serum hepatitis also known as Theiler\u2019s disease has been reported worldwide, causing idiopathic acute hepatitis and liver failure in horses. Recent studies have suggested a novel parvovirus, named equine parvovirus hepatitis (EqPV-H), to be associated with Theiler\u2019s disease. Despite the severity and potential fatality of EqPV-H infection, little is known about the possibility of developing chronic infections and putative cross-species infection of equine sister species. In the present longitudinal study, we employed qPCR analysis, serology, and biochemical testing as well as pathology examination of liver biopsies and sequence analysis to investigate potential chronic EqPV-H infection in an isolated study cohort of in total 124 horses from Germany over five years (2013\u20132018). Importantly, our data suggest that EqPV-H viremia can become chronic in infected horses that do not show biochemical and pathological signs of liver disease. Phylogenetic analysis by maximum likelihood model also confirms high sequence similarity and nucleotide conservation of the multidomain nuclear phosphoprotein NS1 sequences from equine serum samples collected between 2013\u20132018. Moreover, by examining human, zebra, and donkey sera for the presence of EqPV-H DNA and VP1 capsid protein antibodies, we found evidence for cross-species infection in donkey, but not to human and zebra. In conclusion, this study provides proof for the occurrence of persistent EqPV-H infection in asymptomatic horses and cross-species EqPV-H detection in donkeys.<\/jats:p>","DOI":"10.3390\/v13081454","type":"journal-article","created":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T22:22:46Z","timestamp":1627338166000},"page":"1454","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Clinical Course of Infection and Cross-Species Detection of Equine Parvovirus-Hepatitis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3875-0707","authenticated-orcid":false,"given":"Birthe","family":"Reinecke","sequence":"first","affiliation":[{"name":"Institute of Experimental Virology, TWINCORE, a Joint Venture between Hannover Medical School and Helmholtz Centre for Infection Research, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Kl\u00f6hn","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Virology, Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannick","family":"Br\u00fcggemann","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Virology, Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6984-678X","authenticated-orcid":false,"given":"Volker","family":"Kinast","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Virology, Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3564-1014","authenticated-orcid":false,"given":"Daniel","family":"Todt","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Virology, Ruhr-University Bochum, 44801 Bochum, Germany"},{"name":"European Virus Bioinformatics Center (EVBC), 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Stang","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Virology, Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcha","family":"Badenhorst","sequence":"additional","affiliation":[{"name":"Department for Companion Animals and Horses, University of Veterinary Medicine, 1210 Vienna, Austria"},{"name":"Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, Pretoria 0110, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Koeppel","sequence":"additional","affiliation":[{"name":"Department of Production Animal Studies, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, Pretoria 0110, South Africa"},{"name":"Centre for Veterinary Wildlife Studies, Faculty of Veterinary Sciences, University of Pretoria, Onderstepoort, Pretoria 0110, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Guthrie","sequence":"additional","affiliation":[{"name":"Equine Research Centre, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, Pretoria 0110, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Groner","sequence":"additional","affiliation":[{"name":"Economic Cooperative of German Veterinarians e.G. (WDT), 27318 Hoyerhagen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2592-6868","authenticated-orcid":false,"given":"Christina","family":"Puff","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine","family":"de le Roi","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Baumg\u00e4rtner","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8575-7402","authenticated-orcid":false,"given":"Jessika-M. V.","family":"Cavalleri","sequence":"additional","affiliation":[{"name":"Department for Companion Animals and Horses, University of Veterinary Medicine, 1210 Vienna, Austria"},{"name":"Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eike","family":"Steinmann","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Virology, Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,26]]},"reference":[{"key":"ref_1","unstructured":"Theiler, A. (1919). Acute Liver-Atrophy and Parenchymatous Hepatitis in Horses, Union of South Africa, 5th and 6th Reports of the Director of Veterinary Research."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"303","DOI":"10.3201\/eid2402.171031","article-title":"New Parvovirus Associated with Serum Hepatitis in Horses after Inoculation of Common Biological Product","volume":"24","author":"Divers","year":"2018","journal-title":"Emerg. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1111\/j.1939-1676.2005.tb02670.x","article-title":"Serum Hepatitis Associated with Commercial Plasma Transfusion in Horses","volume":"19","author":"Aleman","year":"2005","journal-title":"J. Vet. Intern. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/j.2042-3306.1971.tb04433.x","article-title":"Acute Hepatic Failure in the Horse","volume":"3","author":"Thomsett","year":"1971","journal-title":"Equine Vet. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"E1407","DOI":"10.1073\/pnas.1219217110","article-title":"Identification of a previously undescribed divergent virus from the Flaviviridae family in an outbreak of equine serum hepatitis","volume":"110","author":"Chandriani","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/jvim.15362","article-title":"Viral testing of 10 cases of Theiler\u2019s disease and 37 in-contact horses in the absence of equine biologic product administration: A prospective study (2014\u20132018)","volume":"33","author":"Tomlinson","year":"2019","journal-title":"J. Vet. Intern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11608","DOI":"10.1073\/pnas.1101794108","article-title":"Characterization of a canine homolog of hepatitis C virus","volume":"108","author":"Kapoor","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6171","DOI":"10.1128\/JVI.00250-12","article-title":"Serology-Enabled Discovery of Genetically Diverse Hepaciviruses in a New Host","volume":"86","author":"Burbelo","year":"2012","journal-title":"J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2894","DOI":"10.1099\/jgv.0.000612","article-title":"Proposed update to the taxonomy of the genera Hepacivirus and Pegivirus within the Flaviviridae family","volume":"97","author":"Smith","year":"2016","journal-title":"J. Gen. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Tomlinson, J.E., Wolfisberg, R., Fahn\u00f8e, U., Sharma, H., Renshaw, R.W., Nielsen, L., Nishiuchi, E., Holm, C., Dubovi, E., and Rosenberg, B.R. (2020). Equine pegiviruses cause persistent infection of bone marrow and are not associated with hepatitis. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008677"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1002\/hep.27440","article-title":"Clinical course of infection and viral tissue tropism of hepatitis C virus-like nonprimate hepaciviruses in horses","volume":"61","author":"Pfaender","year":"2015","journal-title":"Hepatology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/eve.13053","article-title":"Theiler\u2019s disease","volume":"32","author":"Divers","year":"2020","journal-title":"Equine Vet. Educ."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1080\/22221751.2020.1741326","article-title":"Tropism, pathology, and transmission of equine parvovirus-hepatitis","volume":"9","author":"Tomlinson","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Meister, T.L., Tegtmeyer, B., Postel, A., Cavalleri, J.-M.V., Todt, D., Stang, A., and Steinmann, E. (2019). Equine Parvovirus-Hepatitis Frequently Detectable in Commercial Equine Serum Pools. Viruses, 11.","DOI":"10.3390\/v11050461"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Baird, J., Tegtmeyer, B., Arroyo, L., Stang, A., Br\u00fcggemann, Y., Hazlett, M., and Steinmann, E. (2020). The association of Equine Parvovirus-Hepatitis (EqPV-H) with cases of non-biologic-associated Theiler\u2019s disease on a farm in Ontario, Canada. Vet. Microbiol., 242.","DOI":"10.1016\/j.vetmic.2019.108575"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1111\/evj.13254","article-title":"First report of equine parvovirus-hepatitis-associated Theiler\u2019s disease in Europe","volume":"52","author":"Vengust","year":"2020","journal-title":"Equine Vet. J."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Lu, G., Sun, L., Ou, J., Xu, H., Wu, L., and Li, S. (2018). Identification and genetic characterization of a novel parvovirus associated with serum hepatitis in horses in China. Emerg. Microbes Infect., 7.","DOI":"10.1038\/s41426-018-0174-2"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lu, G., Wu, L., Ou, J., and Li, S. (2020). Equine Parvovirus-Hepatitis in China: Characterization of Its Genetic Diversity and Evidence for Natural Recombination Events Between the Chinese and American Strains. Front. Vet. Sci., 7.","DOI":"10.3389\/fvets.2020.00121"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1099\/vir.0.042531-0","article-title":"Identification and characterization of bocaviruses in cats and dogs reveals a novel feline bocavirus and a novel genetic group of canine bocavirus","volume":"93","author":"Lau","year":"2012","journal-title":"J. Gen. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1007\/s00705-013-1914-1","article-title":"The family Parvoviridae","volume":"159","author":"Cotmore","year":"2014","journal-title":"Arch. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1007\/s11262-016-1322-1","article-title":"Discovery of a novel Parvovirinae virus, porcine parvovirus 7, by metagenomic sequencing of porcine rectal swabs","volume":"52","author":"Palinski","year":"2016","journal-title":"Virus Genes"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Walter, S., Rasche, A., Moreira-Soto, A., Pfaender, S., Bletsa, M., Corman, V.M., Aguilar-Setien, A., Garc\u00eda-Lacy, F., Hans, A., and Todt, D. (2017). Differential Infection Patterns and Recent Evolutionary Origins of Equine Hepaciviruses in Donkeys. J. Virol., 91.","DOI":"10.1128\/JVI.01711-16"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Burbelo, P.D., Ching, K.H., Klimavicz, C.M., and Iadarola, M.J. (2009). Antibody Profiling by Luciferase Immunoprecipitation Systems (LIPS). JoVE J. Vis. Exp., 7.","DOI":"10.3791\/1549-v"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7552","DOI":"10.1073\/pnas.0802203105","article-title":"Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection","volume":"105","author":"Keele","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1093\/molbev\/msw054","article-title":"MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets","volume":"33","author":"Kumar","year":"2016","journal-title":"Mol. Biol. Evol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/molbev\/msy096","article-title":"MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms","volume":"35","author":"Kumar","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Nei, M., and Kumar, S. (2000). Molecular Evolution and Phylogenetics, Oxford University Press.","DOI":"10.1093\/oso\/9780195135848.001.0001"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"11030","DOI":"10.1073\/pnas.0404206101","article-title":"Prospects for inferring very large phylogenies by using the neighbor-joining method","volume":"101","author":"Tamura","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/nature12323","article-title":"Recalibrating Equus evolution using the genome sequence of an early Middle Pleistocene horse","volume":"499","author":"Orlando","year":"2013","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Meister, T.L., Tegtmeyer, B., Br\u00fcggemann, Y., Sieme, H., Feige, K., Todt, D., Stang, A., Cavalleri, J.V., and Steinmann, E. (2019). Characterization of Equine Parvovirus in Thoroughbred Breeding Horses from Germany. Viruses, 11.","DOI":"10.3390\/v11100965"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Badenhorst, M., Heus, P., Auer, A., Tegtmeyer, B., Stang, A., Dimmel, K., Tichy, A., Kubacki, J., Bachofen, C., and Steinmann, E. (2021). Active equine parvovirus-hepatitis infection is most frequently detected in Austrian horses of advanced age. Equine Vet. J.","DOI":"10.1111\/evj.13444"},{"key":"ref_32","unstructured":"Mittel, L.D., Norton, P., Tomlinson, J.E., and Divers, T.J. (2021, March 25). Equine Parvovirus Hepatitis Virus Control Guidelines. American Association of Equine Practitioners. Available online: https:\/\/aaep.org\/sites\/default\/files\/2021-03\/Equine_Parvovirus_Hepatitis_Virus_Control_Guidelines.pdf."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/8\/1454\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:35:13Z","timestamp":1760164513000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/8\/1454"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,26]]},"references-count":32,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["v13081454"],"URL":"https:\/\/doi.org\/10.3390\/v13081454","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,26]]}}}