HONEY BEES PLAY A VITAL ROLE IN POLLINATION OF CROPS CONTRIBUTING SIGNIFICANTLY TO THE VALUE OF CROP PRODUCTION IN THE UNITED STATES. SEVERE LOSSES OF HONEY BEE COLONIES THREATEN OUR ABILITY TO MEET THE POLLINATION NEEDS OF U.S. AGRICULTURE. WHILE RESEARCH SUGGESTS THAT COLONY LOSSES ARE LIKELY TO RESULT FROM MULTIPLE FACTORS, VIRUSES PLAY A PRIMARY ROLE IN COLONY DECLINE, ALONG WITH THE VARROA MITE, WHICH EXACERBATES VIRUS INFECTION. WE PLAN TO EXAMINE THE FUNDAMENTAL BIOLOGY OF VIRUS INTERACTION WITH THE HONEY BEE WITH A FOCUS ON TWO OF THE MOST IMPORTANT VIRUSES: ISRAELI ACUTE PARALYSIS VIRUS (IAPV) AND DEFORMED WING VIRUS (DWV). WE WILL THEN APPLY THIS KNOWLEDGE TO PREVENT HONEY BEE INFECTION BY THE ORAL ROUTE. SPECIFICALLY WE WILL IDENTIFY THE HONEY BEE GUT PROTEINS, OR RECEPTORS BOUND BY THESE VIRUSES THAT MEDIATE VIRUS ENTRY INTO THE HONEY BEE GUT CELLS. WE WILL ALSO IDENTIFY SMALL PROTEINS, OR PEPTIDES THAT INTERFERE WITH VIRUS-GUT CELL BINDING. WE WILL TEST THE HYPOTHESIS THAT VIRUS ENTRY VIA THE GUT PROVIDES A TARGET FOR INTERVENTION TOWARD SUPPRESSION OF THE DELETERIOUS IMPACT OF VIRUSES ON HONEY BEE SURVIVAL. IN SO DOING, WE WILL INCREASE OUR UNDERSTANDING OF THE MECHANISMS INVOLVED IN HONEY BEE-VIRUS INTERACTION AND DEMONSTRATE THE PRACTICAL APPLICATION OF SUCH KNOWLEDGE TOWARD SUPPRESSION OF VIRUS ENTRY, REDUCTION IN BOTH VIRUS LOAD AND VIRUS-ASSOCIATED MORTALITY TO THE BENEFIT OF HONEY HEALTH.