Pathogenesis, MicroRNA‐122 Gene‐Regulation, and Protective Immune Responses After Acute Equine Hepacivirus Infection

• DOI: 10.1002/hep.31802
• Publication Date: 2021-03-13T16:54:04Z
• Authors: Joy E. Tomlinson; Raphael Wolfisberg; Ulrik Fahnøe; Roosheel S. Patel; Sheetal Trivedi; Arvind Kumar; Himanshu Sharma; Louise Nielsen; Sean P. McDonough; Jens Bukh; Bud C. Tennant; Amit Kapoor; Brad R. Rosenberg; Charles M. Rice; Thomas J. Divers; Gerlinde R. Van d...; Troels K.H. Scheel
• Keywords: Viremia; Pathogenesis; Seroconversion; Liver disease; Hepatitis C

Equine hepacivirus (EqHV) is phylogenetically the closest relative of HCV and shares genome organization, hepatotropism, transient or persistent infection outcome, ability to cause hepatitis. Thus, EqHV studies are important understand equine liver disease further as an outbred surrogate animal model for pathogenesis protective immune responses. Here, we aimed characterize course associated responses.Seven horses were experimentally inoculated with EqHV, monitored 6 months, rechallenged same and, subsequently, a heterologous EqHV. Clearance was primary outcome (6 7) subclinical hepatitis characterized by lymphocytic infiltrate individual hepatocyte necrosis. Seroconversion delayed antibody titers waned slowly. conferred nonsterilizing immunity, resulting in shortened duration viremia after rechallenge. Peripheral blood mononuclear cell responses minimal, although EqHV-specific T cells identified. Additionally, interferon-stimulated gene signature detected during infection, similar acute humans. HCV, stimulated direct binding liver-specific microRNA (miR), miR-122. Interestingly, found that sequesters enough miR-122 functionally affect regulation liver. This RNA-based mechanism thus could have consequences pathology.EqHV typically has resolving course, response lasts at least year broadly attenuates subsequent infections. implications achieve goal vaccine; prevent chronicity while accepting virus exposure.