Equine Hepacivirus Research Could Guide Development of Hepatitis C Vaccine

Hepatitis C virus (HCV) represents a major public health problem, causing acute and chronic disease in an estimated 2.7 million to 3.9 million people in the United States. Although acute infection may be asymptomatic, many affected individuals are unable to clear the virus and subsequently develop chronic infection which may manifest as hepatitis, cirrhosis, and even hepatocellular carcinoma.

However, the recent discovery of novel hepaciviruses in different animal species could help to provide new information about HCV. Non-primate hepaciviruses were first discovered in domestic dogs and later in horses. Indeed, Equine hepacivirus (EHCV) has been identified as the closest known relative to HCV. Now, research to investigate how the horse immune system naturally eliminates EHCV could be used in the quest to develop a vaccine for HCV.

Robert Mealey, DVM, PhD, from Washington State University, and colleagues were recently awarded a grant by the National Institute of Allergy and Infectious Diseases to pursue this research.

EHCV was first reported in the United States in 2012 and is now known to be highly prevalent in horses, with up to 40% of horses infected, and up to 3% having viremia, according to some studies. However, in most cases, EHCV does not cause disease, although several studies have reported subclinical hepatitis in infected horses. Nevertheless, a causative association between EHCV infection and hepatitis has yet to be determined.

In two recent studies, researchers have described the course of naturally-acquired EHCV in horses. In their first study, they followed 20 mare-foal pairs and showed that EHCV can be passed from mares to foals at birth, and also that some foals became viremic within the first six months of life. They also suggested the possibility of direct transmission of the virus between horses.

In their second study, the researchers monitored infections in four of the young horses from the first study, following them until they were about 1-year old. They showed that the EHCV infection progressed from acute to chronic in the young horses during this time. The researchers detected EHCV RNA in the foals at the age of six months. They also showed that the foals remained viremic for another seven months, and also developed antibodies against the virus.

The concentrations of liver specific enzymes in the blood also increased in three of the foals when they were about 1-year-old, but not at any other time point, and horses showed no clinical signs of liver disease at any point.

According to the authors, despite developing antibodies against the virus, the horses did not clear the infection during the study timeframe, and remained chronically infected, although the reason for this was unknown.

A recent study by Dr. Mealey and colleagues highlighted some of the similarities between EHCV and HCV. In particular, their study showed that experimental EHCV infection was associated with acute and chronic liver disease in horses, as demonstrated by increased concentrations of liver-specific enzymes as well as by histopathologic findings such as hepatitis. In addition, consistent with data from some previous studies, the researchers also found that some horses were able to clear EHCV infection.

“These data extend other recent studies and provide the basis for further studies focused on defining the mechanisms of hepacivirus pathogenesis and the correlates of protective immunity, as well as validate EHCV infection in horses as a translational large animal model for HCV,” Dr. Mealey and colleagues conclude.

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.