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Title: Experimental transmission of equine hepacivirus in horses as a model for hepatitis C virus

item RAMSAY, JOSHUA - Washington State University
item EVANOFF, RYAN - Washington State University
item WILKINSON JR, TOM - Washington State University
item DIVERS, THOMAS - Cornell University
item Knowles Jr, Donald
item MEALEY, ROBERT - Washington State University

Submitted to: Hepatology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/10/2015
Publication Date: 2/24/2015
Citation: Ramsay, J.D., Evanoff, R., Wilkinson Jr, T.E., Divers, T.J., Knowles Jr, D.P., Mealey, R.H. 2015. Experimental transmission of equine hepacivirus in horses as a model for hepatitis C virus. Hepatology. 61(5):1533-46.

Interpretive Summary: 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. Diseases related to liver function in horses and humans are important challenges in medicine. This work describes infection of horses with a virus associated with liver disease and presents it as a potential model for studying human liver disease and a causative virus, hepatitis C virus (HCV).

Technical Abstract: Equine hepacivirus (EHCV; non-primate hepacivirus) is a hepatotropic member of the Flaviviridae family that infects horses. Although EHCV is the closest known relative to hepatitis C virus (HCV), its complete replication kinetics in vivo have not been described, and direct evidence that it causes hepatitis has been lacking. In this study we detected EHCV in two horses that developed post-transfusion hepatitis. Plasma and serum from these horses were used to experimentally transmit EHCV to four young adult Arabian horses, two one-month-old foals (one Arabian and one Arabian-pony cross) and two foals (one Arabian and one Arabian-pony 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-specific enzymes and/or by histopathology. Although most of these animals were co-infected 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-pony crosses and one SCID foal were then inoculated with plasma containing only EHCV, and evidence of mild acute hepatocellular damage was observed. The different levels of liver-specific 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.