{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T04:54:01Z","timestamp":1788670441990,"version":"build-2803163510"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T00:00:00Z","timestamp":1623369600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Equine hepacivirus (EqHV) is phylogenetically the closest relative of HCV and shares genome organization, hepatotropism, transient or persistent infection outcome, and the ability to cause hepatitis. Thus, EqHV studies are important to understand equine liver disease and further as an outbred surrogate animal model for HCV pathogenesis and protective immune responses. Here, we aimed to characterize the course of EqHV infection and associated protective immune responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results<\/jats:title>\n                    <jats:p>Seven horses were experimentally inoculated with EqHV, monitored for 6\u00a0months, and rechallenged with the same and, subsequently, a heterologous EqHV. Clearance was the primary outcome (6 of 7) and was associated with subclinical hepatitis characterized by lymphocytic infiltrate and individual hepatocyte necrosis. Seroconversion was delayed and antibody titers waned slowly. Clearance of primary infection conferred nonsterilizing immunity, resulting in shortened duration of viremia after rechallenge. Peripheral blood mononuclear cell responses in horses were minimal, although EqHV\u2010specific T cells were identified. Additionally, an interferon\u2010stimulated gene signature was detected in the liver during EqHV infection, similar to acute HCV in humans. EqHV, as HCV, is stimulated by direct binding of the liver\u2010specific microRNA (miR), miR\u2010122. Interestingly, we found that EqHV infection sequesters enough miR\u2010122 to functionally affect gene regulation in the liver. This RNA\u2010based mechanism thus could have consequences for pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>EqHV infection in horses typically has an acute resolving course, and the protective immune response lasts for at least a year and broadly attenuates subsequent infections. This could have important implications to achieve the primary goal of an HCV vaccine; to prevent chronicity while accepting acute resolving infection after virus exposure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.31802","type":"journal-article","created":{"date-parts":[[2021,3,13]],"date-time":"2021-03-13T11:54:04Z","timestamp":1615636444000},"page":"1148-1163","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":25,"title":["Pathogenesis, MicroRNA\u2010122 Gene\u2010Regulation, and Protective Immune Responses After Acute Equine Hepacivirus Infection"],"prefix":"10.1097","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7365-3967","authenticated-orcid":false,"given":"Joy E.","family":"Tomlinson","sequence":"first","affiliation":[{"name":"Baker Institute for Animal Health,Cornell University College of Veterinary Medicine,Ithaca,NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6191-2084","authenticated-orcid":false,"given":"Raphael","family":"Wolfisberg","sequence":"additional","affiliation":[{"name":"Copenhagen Hepatitis C Program (CO\u2010HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology,University of Copenhagen,Copenhagen,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrik","family":"Fahn\u00f8e","sequence":"additional","affiliation":[{"name":"Copenhagen Hepatitis C Program (CO\u2010HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology,University of Copenhagen,Copenhagen,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0683-6920","authenticated-orcid":false,"given":"Roosheel S.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Microbiology,Icahn School of Medicine at Mount Sinai,New York,NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheetal","family":"Trivedi","sequence":"additional","affiliation":[{"name":"Center for Vaccines and Immunity,Research Institute at Nationwide Children\u2019s Hospital,Columbus,OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvind","family":"Kumar","sequence":"additional","affiliation":[{"name":"Center for Vaccines and Immunity,Research Institute at Nationwide Children\u2019s Hospital,Columbus,OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Himanshu","family":"Sharma","sequence":"additional","affiliation":[{"name":"Center for Vaccines and Immunity,Research Institute at Nationwide Children\u2019s Hospital,Columbus,OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Copenhagen Hepatitis C Program (CO\u2010HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology,University of Copenhagen,Copenhagen,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean P.","family":"McDonough","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences,Cornell University College of Veterinary Medicine,Ithaca,NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7815-4806","authenticated-orcid":false,"given":"Jens","family":"Bukh","sequence":"additional","affiliation":[{"name":"Copenhagen Hepatitis C Program (CO\u2010HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology,University of Copenhagen,Copenhagen,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bud C.","family":"Tennant","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences,Cornell University College of Veterinary Medicine,Ithaca,NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Kapoor","sequence":"additional","affiliation":[{"name":"Center for Vaccines and Immunity,Research Institute at Nationwide Children\u2019s Hospital,Columbus,OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5885-1276","authenticated-orcid":false,"given":"Brad R.","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Department of Microbiology,Icahn School of Medicine at Mount Sinai,New York,NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles M.","family":"Rice","sequence":"additional","affiliation":[{"name":"Laboratory of Virology and Infectious Disease,The Rockefeller University,New York,NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Divers","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences,Cornell University College of Veterinary Medicine,Ithaca,NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerlinde R.","family":"Van de Walle","sequence":"additional","affiliation":[{"name":"Baker Institute for Animal Health,Cornell University College of Veterinary Medicine,Ithaca,NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1545-4067","authenticated-orcid":false,"given":"Troels K.H.","family":"Scheel","sequence":"additional","affiliation":[{"name":"Copenhagen Hepatitis C Program (CO\u2010HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology,University of Copenhagen,Copenhagen,Denmark"},{"name":"Laboratory of Virology and Infectious Disease,The Rockefeller University,New 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