**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 VIRAL DIARRHEA VIRUS (BVDV)IS A FINANCIALLY IMPORTANT PATHOGEN OF THE CATTLE INDUSTRY. BILLIONS OF DOLLARS OF PROFIT ARE SACRIFICEDGLOBALLY EACH YEAR TO REPRODUCTIVE FAILURES AND PRODUCTION LOSSES ASSOCIATED WITH THE DISEASE. BVDV IS ALSO KNOWN TO CONTRIBUTE SIGNIFICANTLY TO THE DEVELOPMENT OF BOVINE RESPIRATORY DISEASE (BRD) IN CATTLE, INCURRING ANOTHER 800 MILLION DOLLARS IN COST. BVDV IS ESPECIALLY UNIQUE IN ITS ABILITY TO BE TRANSMITTED VERTICALLY, FROM MOTHER TO BABY; WHEN A PREGNANT COW IS INFECTED, THE DEVELOPING FETUS ALSO BECOMES INFECTED. INFECTIONS OCCURRING VERY EARLY IN GESTATION CAN RESULT IN EMBRYO MORTALITYOR ABORTION. INFECTIONS OCCURING PRIOR TO 125 DAYS OF GESTATION THAT DO NOT RESULT IN FETAL DEATH GENERATE A PERSISTENTLY INFECTED (PI) CALFIN UTERO. BECAUSE INFECTION OCCURS PRIOR TO COMPETENCE OF THEIMMUNE SYSTEM, PI CALVES DO NOT RECOGNIZE THE VIRUS AS FOREGIN AND DO NOT PRODUCE ANTIBODIES AGAINST THE PATHOGEN. INFECTION OCCURRING LATER IN GESTATION, AFTER 150 DAYS, RESULTS IN THE GENERATION OF A TRANSIENTLY INFECTED (TI) CALF. BY 150 DAYS OF GESTATION, THE FETAL IMMUNE SYSTEM IS ABLE TO MOUNT A MORE COMPLETE IMMUNE RESPONSE TO THE PATHOGEN, PRODUCE ANTIBODIES AGAINST THE VIRUS, AND ULTIMATELY OVERCOME THE INFECTION PRIOR TO BIRTH. WHILE THE CONSEQUENCES OF INFECTION IN FETUSES PRIOR TO 125 DAYS OF GESTATION IS WELL RESEARCHED, TI CALVES REMAIN AN AREA OF DEBATE. PREVIOUS RESEARCHSUGGESTS THAT INFECTION DURING FETAL DEVELOPMENT, A PERIOD IN WHICH ALL GROWTH IS CRITICAL TO DEVELOPMENT OF THE FETUS, EXPOSURE TO A PATHOGEN COULD INFLUENCE THE PHYSIOLOGICAL FUNCTION OF THE INDIVIDUAL AFTER BIRTH. IN FACT, PREVIOUS DATA INDICATES THAT CATTLE INFECTED WITH BVDV DURING FETAL DEVLEOPMENT EXPERIENCE ALTERATIONS IN DNA ACCESSIBILITY BOTH AT 245 DAYS OF GESTATION AND 4 MONTHS AFTER BIRTH. AS SUCH, THIS PROJECT AIMS TO CONFIRM THAT THESE CHANGES ARE STILL PRESENT IN ANIMALS OF ADULT AGE (17 MONTHS). DNA METHYLATION DATA WILL DEMONSTRATE DIFFERENCES IN DNA ACCESSIBILITY WHILE SINGLE CELL RNA SEQUENCING WILL PROVIDE A DETAILED LOOK INTO DIFFERENCES IDENTIFIED IN CELLULAR PRODUCTION OF TRANSCRIPTS. INVESTIGATING TI CATTLE ON THE EPIGENETIC LEVEL CAN INDICATE THE PHYSIOLOGICAL ALTERATIONS THESE CATTLE EXPERIENCE AS A RESULT OF FETAL BVDV INFECTION. PROPER ASSESSMENT OF THE TRUE LOSS DUE TO BVDV, IN THE FORM OF APPRAISING THE LOSS DUE TO TI CATTLE, WILL ENCOURAGE PROGRESS IN THE SCIENTIFIC COMMUNITY TO DEVELOP TREATMENTS AND VACCINATIONS FOR THE PATHOGEN .ADDITIONALLY, CHARACTERIZATION OF DYSFUNCTION IDENTIFIED IN TI CATTLE WILL CONTRIBUTE TO A STRONGER RATIONALE FOR THE IDENTIFICATION, APPROPRIATE THERAPEUTIC MANAGEMENT, AND THE ELIMINATION OF BVDV.