Experimental transmission of equine hepacivirus in horses as a model for hepatitis C virus.
Abstract: Equine hepacivirus (EHCV; nonprimate 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 2 horses that developed post-transfusion hepatitis. Plasma and serum from these horses were used to experimentally transmit EHCV to 4 young adult Arabian horses, two 1-month-old foals (1 Arabian and 1 Arabian-pony cross), and 2 foals (1 Arabian and 1 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 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-pony 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-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. Conclusions: 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.
© 2015 by the American Association for the Study of Liver Diseases.
Publication Date: 2015-02-24 PubMed ID: 25580897DOI: 10.1002/hep.27689Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The researchers of this study explored how equine hepacivirus (EHCV), a virus similar to the hepatitis C virus (HCV) in humans and found in horses, could be transmitted and cause liver disease. The experiment involved infecting different breeds and ages of horses with the EHCV, studying the virus’s infection kinetics (how it spreads and replicates in the body), comparing it to HCV, and observing for signs of liver disease.
Study Design and Methodology
- The researchers observed two horses that had developed post-transfusion hepatitis and detected EHCV in these animals.
- They then utilized the plasma and serum from the infected horses to experimentally transmit EHCV to four young adult Arabian horses, two foals of different breeds, and two foals with severe combined immunodeficiency (SCID).
- Three additional young Arabian-pony crosses and a SCID foal were given plasma containing only EHCV to provide further data and prove that the virus itself caused the liver disease.
Results and Findings
- The study found that the EHCV infection and replication kinetics were similar to those of HCV.
- Evidence of acute and chronic liver disease was observed in infected horses through elevated liver-specific enzymes and changes in liver tissues – indicative of pathology.
- Interestingly, some horses were coinfected with equine pegivirus (EPgV), another virus from the Flaviviridae family, but the negative impact from this coinfection wasn’t as severe.
- There were variations in liver-specific enzyme elevation, inflammation, and the duration of viremia (presence of viruses in the blood), and these changes were attributed to factors such as virus load, horse breed, age, and immune status.
Conclusion & Implication
- The study confirmed that EHCV is a cause of liver disease in horses, similar to the role of HCV in humans.
- The findings provide a new perspective on the EHCV infection process, from kinetics and replication to the resulting liver pathology.
- This research could also be valuable in studying HCV in humans by using the horse as a large animal model for the virus. The discovered similarities between EHCV and HCV might offer insight into the human version of the virus and help develop treatment strategies.
Cite This Article
APA
Ramsay JD, Evanoff R, Wilkinson TE, Divers TJ, Knowles DP, Mealey RH.
(2015).
Experimental transmission of equine hepacivirus in horses as a model for hepatitis C virus.
Hepatology, 61(5), 1533-1546.
https://doi.org/10.1002/hep.27689 Publication
Researcher Affiliations
- Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA.
MeSH Terms
- Animals
- Disease Models, Animal
- Hepatitis C, Chronic / transmission
- Hepatitis C, Chronic / veterinary
- Horse Diseases / transmission
- Horse Diseases / virology
- Horses
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