**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** BOVINE HERPESVIRUS 1 (BOHV-1) IS A MAJOR CATTLE PATHOGEN THAT CONTRIBUTES TO BOVINE RESPIRATORY DISEASE COMPLEX, WHICH RESULTS IN ECONOMIC LOSSES EXCEEDING $5 BILLION EACH YEAR. ADDITIONALLY, BOHV-1 CAUSES ABORTIONS IN INFECTED COWS, CAUSING MAJOR LOSSES IN BREEDING AND THE DAIRY INDUSTRY. THE PRIMARY DIFFICULTY IN CONTROLLING BOHV-1 INFECTION IS ITS INFECTION LIFECYCLE. AFTER INFECTING A NEW HOST, THE VIRUS ESTABLISHES A LIFELONG LATENT INFECTION IN SENSORY NEURONS, MAKING THIS VIRUS NEARLY IMPOSSIBLE TO CURE. THIS LATENCY IS MARKED BE PERIODIC REACTIVATION, LEADING TO ACUTE DISEASE SYMPTOMS, INCLUDING RESPIRATORY DISEASE AND REPRODUCTIVE FAILURE. DURING ACUTE INFECTION, THE VIRUS CAN BE READILY PASSED BETWEEN COWS. REACTIVATION OCCURS MORE READILY DURING PERIODS OF ELEVATED STRESS, PARTICULARLY DURING TRANSPORT. AS A RESULT, INFECTED COWS ARE MORE LIKELY TO SPREAD BOHV-1 AT PRECISELY THE TIME THEY ARE IN CONTACT WITH THE MOST OTHER COWS. IN THE UNITED STATES, MOST COWS ARE TRANSPORTED BETWEEN FEEDLOTS OR OTHER SITES SEVERAL TIMES EACH YEAR. THERE EXIST TWO COMMERCIAL VACCINES, BUT THESE HAVE NOT ELIMINATED THE VIRUS, AND IN SOME CASES CAN INCREASE ABORTION RATES IN COWS.OUR GOAL IS TO REDUCE THE SPREAD OF BOHV-1 BY BLOCKING REACTIVATION, MUCH LIKE HOW MANY HUMAN HERPESVIRUSES ARE CONTROLLED. SINCE STRESS IS A MAJOR DRIVER OF REACTIVATION, WE HAVE IDENTIFIED SEVERAL KEY PROTEINS THAT INCREASE BOHV-1 PRODUCTIVE INFECTION, AND REACTIVATION. KEY AMONG THESE IS THE GLUCOCORTICOID RECEPTOR (GR), A PROTEIN EXPRESSED IN MOST CELL TYPES THAT DRIVES THE CELLULAR STRESS RESPONSE, IN REACTION TO SPECIFIC HORMONES, CALLED CORTICOSTEROIDS. WE ARE DISSECTING THE MECHANISMS THAT BOHV-1 USES TO HIJACK GR INTO DRIVING ITS OWN GENE EXPRESSION AND PRODUCTIVE INFECTION. FROM THERE, WE ARE TRYING TO BLOCK REACTIVATION TO DECREASE BOHV-1 SPREAD. THIS PROJECT SPECIFICALLY WILL IDENTIFY HOW GR DRIVES BOHV-1 GENE EXPRESSION, AND WHAT VIRUS PROTEINS ARE EXPRESSED EARLY DURING REACTIVATION.WE MUST KNOW THESE KEY STEPS TO DEVELOP THERAPEUTICS TARGETING REACTIVATION. IF WE CAN EFFECTIVELY REDUCE BOHV-1 REACTIVATION IN INFECTED COWS, WE CAN DRASTICALLY REDUCE VIRUS SPREAD, WHICH WILL LEAD TO IMPROVED HEALTH OUTCOMES IN CATTLE, REDUCE ECONOMIC LOSSES, AND INCREASE INDUSTRY STABILITY. THESE ARE VERY IMPORTANT GOALS FOR THE LARGE CATTLE INDUSTRY IN THE UNITED STATES, AND BEYOND.