DESPITE MAJOR ADVANCES IN CONTROLLING MAREK'S DISEASE (MD) BY GENETIC RESISTANCE AND VACCINATION, HISTORY SUGGESTS THAT THE VIRUS WILL LIKELY EVOLVE TOWARDS HIGHER VIRULENCE, WHICH WILL EVENTUALLY LEAD TO ANOTHER DISEASE OUTBREAK. THUS, THIS PROPOSAL ADDRESSES THE CRITICAL NEED FOR A LONG-TERM AND SUSTAINABLE SOLUTION TO STOP OR SLOW DOWN THE CYCLE OF VIRAL EVOLUTION TO HIGHER VIRULENCE IN ORDER TO DELAY THE NEED TO DEVELOP AND INTRODUCE A NEW SET OF MORE EFFECTIVE VACCINES. THE ULTIMATE GOAL IS NOT ONLY TO SELECT FOR REDUCED DISEASE INCIDENCE AND IMPROVED MD VACCINES BUT ALSO FOR BREEDERS AND VACCINE MANUFACTURERS TO SELECT FOR REDUCED VIRUS TRANSMISSION, IN ORDER TO REDUCE VIRUS LOAD IN THE ENVIRONMENT AND LOWER THE OPPORTUNITY FOR VIRUS EVOLUTION.WE PLAN TO ACHIEVE THESE GOALS THROUGH A SERIES OF EXPERIMENTS THAT DETERMINE INFECTIVITY OF DONOR BIRDS BASED ON RESPONSE OF CONTACT RECIPIENT BIRDS. IN OBJECTIVES 1 & 2, WE EXAMINE 1) HOW LONG RECIPIENT BIRDS NEED TO BE EXPOSED TO A VIRUS-SHEDDING DONOR BIRD TO ALLOW INFECTION OF THE RECIPIENT BIRDS, 2) INITIATION AND DURATION OF DONOR VIRUS TRANSMISSION FOR MULTIPLE GENETIC BACKGROUNDS AND VACCINATIONS, 3) THE EFFECT OF HOST GENETICS AND VACCINATION ON INFECTIVITY USING MANY REPLICATES TO ACHIEVE ADEQUATE STATISTICAL POWER, AND 4) DETERMINATION OF WHETHER MD GENETIC RESISTANCE OR MD VACCINES SIGNIFICANTLY ALTER FFE VIRAL LOAD. SAMPLES TO BE COLLECTED INCLUDE FEATHERS FROM DONOR AND RECIPIENT BIRDS AT MULTIPLE TIME POINTS, AS WELL AS BLOOD FROM RECIPIENT BIRDS. THE THOUSANDS OF SAMPLES COLLECTED WILL NOT ONLY ALLOW US TO DETERMINE WHEN RECIPIENT BIRDS BECOME INFECTED, WE CAN ALSO DETERMINE IF VIRAL LOAD IN DONOR FEATHERS CAN SERVE AS A PROXY INDICATOR OF INFECTIVITY. IF ONE ASSUMES THAT REDUCING VIRAL LOAD IN THE POULTRY HOUSE IS RELEVANT FOR SUSTAINABLE MD CONTROL, BY REDUCING THE LIKELIHOOD THAT MORE VIRULENT MDV STRAINS WILL EMERGE, THEN ONE OF THE MAJOR CHALLENGES WILL BE HOW TO SELECT BIRDS OR VACCINES FOR REDUCED TRANSMISSION. OBJECTIVE 3 FURTHER DISSECTS THE RELATIONSHIP BETWEEN GENETIC RESISTANCE AND VIRAL LOAD IN FFE IN ORDER TO PROVIDE INITIAL INSIGHTS ABOUT GENETIC REGIONS POTENTIALLY ASSOCIATED WITH VIRUS TRANSMISSION. THESE INSIGHTS WILL ALLOW FUTURE GENETIC SELECTION TO BE MADE FOR BOTH REDUCED DISEASE INCIDENCE AND REDUCED VIRUS TRANSMISSION.WE BELIEVE THIS WORK WILL GENERATE CRUCIAL UNDERSTANDING OF HOW VACCINATION AND HOST GENETICS INFLUENCE MD SPREAD IN POULTRY POPULATIONS. THE RESULTING INFORMATION WILL PROVIDE BREEDERS, BIOLOGIC COMPANIES, AND POLICY MAKERS WITH NEW SUSTAINABLE OPPORTUNITIES FOR PRACTICAL INTERVENTIONS TO CONTROL MD BY TARGETING BOTH OF THE KEY EPIDEMIOLOGICAL TRAITS AFFECTING DISEASE RISK AND SEVERITY IN POULTRY POPULATIONS: HOST RESISTANCE AND INFECTIVITY. THE LONG-TERM GOALS OF THIS STUDY, BY IDENTIFYING PHENOTYPIC AND ULTIMATELY GENETIC MARKERS FOR REDUCED VIRUS TRANSMISSION, ARE TO REDUCE ENVIRONMENTAL VIRUS LOAD AND THUS INCREASE EXISTING AND FUTURE VACCINE EFFICACY. WE BELIEVE THAT THE TOOLS AND INSIGHTS FOR ASSESSING THE RELATIONSHIP BETWEEN HOST RESISTANCE AND INFECTIVITY WILL BE USEFUL FOR OTHER TYPES OF INFECTIOUS DISEASES IN DIFFERENT SPECIES.