EQUINE HEPACIVIRUS (EQHV) IS A VERY COMMON VIRUS AND WE HAVE RECENTLY OBSERVED THAT IT CANCAUSE DEADLY HEPATITIS (LIVER DISEASE) IN HORSES. THIS CONDITION STRONGLY RESEMBLES LIVER DISEASE CAUSED BY THE CLOSELY RELATED HEPATITIS C VIRUS (HCV) IN HUMANS. GIVEN THIS INCREASED RECOGNITION OF THE HEALTH BURDEN OF EQHV INFECTION IN HORSES, OUR LONG-TERM OBJECTIVE IS TO REDUCE AND/OR PREVENT TRANSMISSION AND DISEASE CAUSED BY EQHV. OUR SPECIFIC HYPOTHESIS IS THAT EQHV IS READILY TRANSMITTED AMONG HORSES AND CAN CAUSE CHRONIC HEPATITIS AND LIVER FAILURE DURING PERSISTENT INFECTION. TO TEST THIS, WE WILL(1) MODEL EQHV INFECTION AND TRANSMISSION BY MONITORING INFECTION IN HORSE HERDS OVER 5 YEARS AND TESTING THE ABILITY OF MOSQUITOES TO CARRY EQHV, (2) CHARACTERIZE THE CLINICAL CONDITION OF CHRONIC EQHV HEPATITIS BY SERIAL TESTING OF AFFECTED HORSES OVER TIME AND EXAMINATION OF BANKED LIVER BIOPSIES, AND (3) IDENTIFY RISK FACTORS OF PERSISTENCE AND SEVERE DISEASE INCLUDING AGE, SEX, HOST IMMUNE RESPONSE, AND VIRAL GENETICS BY COMPARING HORSES THAT CLEAR THE INFECTION WITHOUT SERIOUS ILLNESS AND THOSE THAT DEVELOP CHRONIC INFECTION ANDHEPATITIS.THE SIGNIFICANCE OF THIS WORK IS TO DEVELOP A FOUNDATION FOR EQHV DISEASE DIAGNOSIS, PREVENTION, AND CONTROL. DETERMINING THE TRANSMISSION AND DISEASE BURDEN OF THE VIRUS, AND RISK FACTORS FOR SEVERE DISEASE, CAN DRIVE FUTURE DEVELOPMENT OF VACCINES, TREATMENTS, AND MANAGEMENT STRATEGIES, INCLUDING POSSIBLE GOVERNMENTAL REGULATIONS ON EQUINE BIOLOGIC PRODUCTS, AS HAS BEEN DONE FOR THE OTHER RECENTLY DISCOVERED LIVER PATHOGEN, EQUINE PARVOVIRUS-HEPATITIS. AS SUCH, THIS WORK CAN CONTRIBUTE TO AN OVERALL UNDERSTANDING OF AND REDUCTION IN CASES OF TRANSMISSIBLE LIVER DISEASE IN HORSES WITH HITHERTO UNKNOWN ETIOLOGY.