EQUINE HEPACIVIRUS (EQHV) IS A VERY COMMON VIRUS AND WE HAVE RECENTLY OBSERVED THAT IT CAN CAUSE DEADLY HEPATITIS (LIVERDISEASE) IN HORSES. THIS CONDITION STRONGLY RESEMBLES LIVER DISEASE CAUSED BY THE CLOSELY RELATED HEPATITIS C VIRUS (HCV) INHUMANS. GIVEN THIS INCREASED RECOGNITION OF THE HEALTH BURDEN OF EQHV INFECTION IN HORSES, OUR LONG-TERM OBJECTIVE IS TOREDUCE AND/OR PREVENT TRANSMISSION AND DISEASE CAUSED BY EQHV. OUR SPECIFIC HYPOTHESIS IS THAT EQHV IS READILY TRANSMITTEDAMONG HORSES AND CAN CAUSE CHRONIC HEPATITIS AND LIVER FAILURE DURING PERSISTENT INFECTION. TO TEST THIS, WE WILL (1) MODEL EQHVINFECTION AND TRANSMISSION BY MONITORING INFECTION IN HORSE HERDS OVER 4 YEARS AND TESTING THE ABILITY OF MOSQUITOES TO CARRYEQHV, (2) CHARACTERIZE THE CLINICAL CONDITION OF CHRONIC EQHV HEPATITIS BY SERIAL TESTING OF AFFECTED HORSES OVER TIME ANDEXAMINATION OF DIAGNOSTIC LIVER BIOPSIES, AND (3) IDENTIFY RISK FACTORS OF PERSISTENCE AND SEVERE DISEASE INCLUDING AGE, SEX, HOSTIMMUNE RESPONSE, AND VIRAL GENETICS BY COMPARING HORSES THAT CLEAR THE INFECTION WITHOUT SERIOUS ILLNESS AND THOSE THAT DEVELOPCHRONIC INFECTION AND HEPATITIS. 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 FUTUREDEVELOPMENT OF VACCINES, TREATMENTS, AND MANAGEMENT STRATEGIES, INCLUDING POSSIBLE GOVERNMENTAL REGULATIONS ON EQUINEBIOLOGIC PRODUCTS, AS HAS BEEN DONE FOR THE OTHER RECENTLY DISCOVERED LIVER PATHOGEN, EQUINE PARVOVIRUS-HEPATITIS. AS SUCH, THISWORK CAN CONTRIBUTE TO AN OVERALL UNDERSTANDING OF AND REDUCTION IN CASES OF TRANSMISSIBLE LIVER DISEASE IN HORSES WITH HITHERTOUNKNOWN ETIOLOGY.