{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:44:28Z","timestamp":1790628268807,"version":"4.1.0"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":189,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:p>Equine hepacivirus (EHCV; nonprimate hepacivirus) is a hepatotropic member of the<jats:italic toggle=\"yes\">Flaviviridae<\/jats:italic>family that infects horses. Although EHCV is the closest known relative to hepatitis C virus (HCV), its complete replication kinetics<jats:italic toggle=\"yes\">in vivo<\/jats:italic>have not been described, and direct evidence that it causes hepatitis has been lacking. In this study, we detected EHCV in 2 horses that developed post\u2010transfusion hepatitis. Plasma and serum from these horses were used to experimentally transmit EHCV to 4 young adult Arabian horses, two 1\u2010month\u2010old foals (1 Arabian and 1 Arabian\u2010pony cross), and 2 foals (1 Arabian and 1 Arabian\u2010pony cross) with severe combined immunodeficiency (SCID). Our results demonstrated that EHCV had infection kinetics similar to HCV and that infection was associated with acute and chronic liver disease as measured by elevations of liver\u2010specific enzymes and\/or by histopathology. Although most of these animals were coinfected with equine pegivirus (EPgV), also a flavivirus, EPgV viral loads were much lower and often undetectable in both liver and blood. Three additional young adult Arabian\u2010pony crosses and 1 SCID foal were then inoculated with plasma containing only EHCV, and evidence of mild hepatocellular damage was observed. The different levels of liver\u2010specific enzyme elevation, hepatic inflammation, and duration of viremia observed during EHCV infection suggested that the magnitude and course of liver disease was mediated by the virus inoculum and\/or by host factors, including breed, age, and adaptive immune status.<jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: This work documents the complete infection kinetics and liver pathology associated with acute and chronic EHCV infection in horses and further justifies it as a large animal model for HCV. (H<jats:sc>epatology<\/jats:sc>2015;61:1533\u20131546)<\/jats:p>","DOI":"10.1002\/hep.27689","type":"journal-article","created":{"date-parts":[[2015,1,10]],"date-time":"2015-01-10T09:40:47Z","timestamp":1420882847000},"page":"1533-1546","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":102,"title":["Experimental transmission of equine hepacivirus in horses as a model for hepatitis C virus"],"prefix":"10.1097","volume":"61","author":[{"given":"Joshua D.","family":"Ramsay","sequence":"first","affiliation":[{"name":"Department of Veterinary Microbiology and Pathology,Washington State University,Pullman,WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Evanoff","sequence":"additional","affiliation":[{"name":"Department of Veterinary Microbiology and Pathology,Washington State University,Pullman,WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom E.","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences,Washington State University,Pullman,WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Divers","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine,Cornell University,Ithaca,NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald P.","family":"Knowles","sequence":"additional","affiliation":[{"name":"Department of Veterinary Microbiology and Pathology,Washington State University,Pullman,WA"},{"name":"Animal Disease Research Unit, Agricultural Research Service,U.S. Department of Agriculture,Pullman,WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Mealey","sequence":"additional","affiliation":[{"name":"Department of Veterinary Microbiology and Pathology,Washington State University,Pullman,WA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2015,2,24]]},"reference":[{"key":"hep27689-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1053\/j.gastro.2012.02.016","article-title":"Animal models for the study of hepatitis C virus infection and related liver disease","volume":"142","year":"2012","journal-title":"Gastroenterology"},{"key":"hep27689-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1038\/nm.3183","article-title":"Current progress in development of hepatitis C virus vaccines","volume":"19","year":"2013","journal-title":"Nat Med"},{"key":"hep27689-bib-0004-20241017","doi-asserted-by":"crossref","first-page":"6171","DOI":"10.1128\/JVI.00250-12","article-title":"Serology\u2010enabled discovery of genetically diverse hepaciviruses in a new host","volume":"86","year":"2012","journal-title":"J Virol"},{"key":"hep27689-bib-0005-20241017","doi-asserted-by":"crossref","first-page":"7185","DOI":"10.1128\/JVI.00324-13","article-title":"Identification of a pegivirus (GB virus\u2010like virus) that infects horses","volume":"87","year":"2013","journal-title":"J Virol"},{"key":"hep27689-bib-0006-20241017","first-page":"e00216","article-title":"Identification of rodent homologs of hepatitis C virus and pegiviruses","volume":"4","year":"2013","journal-title":"MBio"},{"key":"hep27689-bib-0007-20241017","doi-asserted-by":"crossref","first-page":"e1003438","DOI":"10.1371\/journal.ppat.1003438","article-title":"Evidence for novel hepaciviruses in rodents","volume":"9","year":"2013","journal-title":"PLoS Pathog"},{"key":"hep27689-bib-0008-20241017","first-page":"E1407","article-title":"Identification of a previously undescribed divergent virus from the Flaviviridae family in an outbreak of equine serum hepatitis","volume":"110","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"hep27689-bib-0009-20241017","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.3201\/eid1812.120498","article-title":"Nonprimate hepaciviruses in domestic horses, United kingdom","volume":"18","year":"2012","journal-title":"Emerg Infect Dis"},{"key":"hep27689-bib-0010-20241017","article-title":"Clinical course of infection and viral tissue tropism of hepatitis C virus\u2010like non\u2010primate hepaciviruses","year":"2014","journal-title":"Hepatology"},{"key":"hep27689-bib-0011-20241017","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1556\/avet.2014.011","article-title":"Non\u2010primate hepacivirus infection with apparent hepatitis in a horse\u2014short communication","volume":"62","year":"2014","journal-title":"Acta Vet Hung"},{"key":"hep27689-bib-0012-20241017","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/0090-1229(75)90080-X","article-title":"Combined immunodeficiency in horses: characterization of the lymphocyte defect","volume":"3","year":"1975","journal-title":"Clin Immunol Immunopathol"},{"key":"hep27689-bib-0013-20241017","doi-asserted-by":"crossref","first-page":"3073","DOI":"10.1128\/jvi.62.8.3073-3076.1988","article-title":"Immune responses are required to terminate viremia in equine infectious anemia lentivirus infection","volume":"62","year":"1988","journal-title":"J Virol"},{"key":"hep27689-bib-0014-20241017","doi-asserted-by":"crossref","first-page":"11485","DOI":"10.1073\/pnas.92.25.11485","article-title":"Equine severe combined immunodeficiency: a defect in V(D)J recombination and DNA\u2010dependent protein kinase activity","volume":"92","year":"1995","journal-title":"Proc Natl Acad Sci U S A"},{"key":"hep27689-bib-0015-20241017","doi-asserted-by":"crossref","first-page":"e44713","DOI":"10.1371\/journal.pone.0044713","article-title":"Re\u2010emergence of the apicomplexan Theileria equi in the United States: elimination of persistent infection and transmission risk","volume":"7","year":"2012","journal-title":"PLoS One"},{"key":"hep27689-bib-0016-20241017","doi-asserted-by":"crossref","first-page":"354","DOI":"10.2460\/ajvr.1984.45.02.354","article-title":"Effect of age on liver enzyme activities in serum of healthy quarter horses","volume":"45","year":"1984","journal-title":"Am J Vet Res"},{"key":"hep27689-bib-0017-20241017","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.2460\/ajvr.1986.47.11.2461","article-title":"Increase of serum gamma\u2010glutamyltransferase in neonatal Standardbred foals","volume":"47","year":"1986","journal-title":"Am J Vet Res"},{"key":"hep27689-bib-0018-20241017","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1084\/jem.194.10.1395","article-title":"Determinants of viral clearance and persistence during acute hepatitis C virus infection","volume":"194","year":"2001","journal-title":"J Exp Med"},{"key":"hep27689-bib-0019-20241017","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1002\/hep.20239","article-title":"Hepatitis C virus kinetics and host responses associated with disease and outcome of infection in chimpanzees","volume":"39","year":"2004","journal-title":"Hepatology"},{"issue":"3 Suppl 1","key":"hep27689-bib-0020-20241017","first-page":"15S","article-title":"Hepatitis C: the clinical spectrum of disease","volume":"26","year":"1997","journal-title":"Hepatology"},{"issue":"11 Suppl 2","key":"hep27689-bib-0021-20241017","first-page":"S32","article-title":"Early recurrence of hepatitis C virus infection after liver transplantation","volume":"12","year":"2006","journal-title":"Liver Transpl"},{"key":"hep27689-bib-0022-20241017","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/j.1365-2893.2009.01172.x","article-title":"Clearance of hepatitis C in chimpanzees is associated with intrahepatic T\u2010cell perforin expression during the late acute phase","volume":"17","year":"2010","journal-title":"J Viral Hepat"},{"key":"hep27689-bib-0023-20241017","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.1128\/JVI.72.4.2589-2599.1998","article-title":"Analysis of hepatitis C virus\u2010inoculated chimpanzees reveals unexpected clinical profiles","volume":"72","year":"1998","journal-title":"J Virol"},{"key":"hep27689-bib-0024-20241017","doi-asserted-by":"crossref","first-page":"15661","DOI":"10.1073\/pnas.202608299","article-title":"Viral and immunological determinants of hepatitis C virus clearance, persistence, and disease","volume":"99","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"hep27689-bib-0025-20241017","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/jmv.10405","article-title":"Clinical features and progression of perinatally acquired hepatitis C virus infection","volume":"70","year":"2003","journal-title":"J Med Virol"},{"key":"hep27689-bib-0026-20241017","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.vetimm.2009.12.004","article-title":"Current understanding of the equine immune response to Rhodococcus equi. An immunological review of R. equi pneumonia","volume":"135","year":"2010","journal-title":"Vet Immunol Immunopathol"},{"issue":"Suppl 1","key":"hep27689-bib-0027-20241017","first-page":"S3","article-title":"Liver biopsy assessment in chronic viral hepatitis: a personal, practical approach","volume":"20","year":"2007","journal-title":"Mod Pathol"},{"key":"hep27689-bib-0028-20241017","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nri1573","article-title":"Immunology of hepatitis B virus and hepatitis C virus infection","volume":"5","year":"2005","journal-title":"Nat Rev Immunol"},{"key":"hep27689-bib-0029-20241017","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/hep.510290121","article-title":"Dynamics of GB virus C viremia early after orthotopic liver transplantation indicates extrahepatic tissues as the predominant site of GB virus C replication","volume":"29","year":"1999","journal-title":"Hepatology"},{"key":"hep27689-bib-0030-20241017","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1099\/vir.0.063016-0","article-title":"Human pegivirus RNA is found in multiple blood mononuclear cells in vivo and serum\u2010derived viral RNA\u2010containing particles are infectious in vitro","volume":"95","year":"2014","journal-title":"J Gen Virol"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.27689","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201505000-00015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T17:30:41Z","timestamp":1747416641000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201505000-00015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,24]]},"references-count":29,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.27689","relation":{},"ISSN":["0270-9139","1527-3350"],"issn-type":[{"value":"0270-9139","type":"print"},{"value":"1527-3350","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2,24]]},"assertion":[{"value":"2014-03-21","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-12-31","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}