** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** HONEY BEES ARE IMPORTANT POLLINATORS OF FRUIT, NUT, OILSEED, AND VEGETABLE CROPS. HIGH ANNUAL LOSSES OF HONEY BEE COLONIES, WHICH HAVE AVERAGED ~38% IN THE US SINCE 2008, ARE ASSOCIATED WITH MULTIPLE ABIOTIC AND BIOTIC FACTORS, INCLUDING VIRUSES. THERE ARE CURRENTLY NO ANTIVIRAL TREATMENTS FOR HONEY BEES AND OUR UNDERSTANDING OF THE IMMUNE DEFENSE MECHANISMS THAT HONEY BEES HAVE EVOLVED TO COMBAT VIRAL INFECTIONS IS LIMITED.TO ADDRESS THIS PROBLEM, WE WILL PERFORM RESEARCH THAT DETERMINES THE VIRUS-LIMITING EFFICACY OF IMMUNE STIMULATORY COMPOUNDS (I.E., THYME OIL/THYMOL OR POLY(I:C)) IN HONEY BEES EXPERIMENTALLY INFECTED WITH THREE DIFFERENT VIRAL PATHOGENS THAT ARE ASSOCIATED WITH HONEY BEE DEATHS (I.E., DEFORMED WING VIRUS, ISRAELI ACUTE PARALYSIS VIRUS, AND SACBROOD VIRUS). THE LABORATORY-BASED STUDIES PLANNED FOR THIS PROJECT ARE REQUIRED TO DETERMINE THE MOST EFFICACIOUS TREATMENTS PRIOR TO FUTURE STUDIES THAT WILL REQUIRE SAMPLES FROM HUNDREDS OF HONEY BEE COLONIES. IN ADDITIONTO FURTHERING THE DEVELOPMENT OF PROMISING BIOLOGICALLY BASED IMMUNOSTIMULATORY COMPOUNDS TO REDUCE HONEY BEE VIRUS INFECTION LEVELS, WE WILL IDENTIFY POTENTIAL UNINTENDED CONSEQUENCES OF EXPOSING HONEY BEES TO EITHER THYME OIL/THYMOL OR POLY(I:C) BY DETERMINING THEIR IMPACTS ON HONEY BEE GENE EXPRESSION, AN INDICATOR OF BEE HEALTH AND PHYSIOLOGY. GENE EXPRESSION STUDIES WILL ALSO FURTHER OUR UNDERSTANDING OF HONEY BEE ANTIVIRAL DEFENSE MECHANISMS.THIS PROJECT DIRECTLY ADDRESSES THE USDA-AFRI A1113 PROGRAM GOALS TO GAIN A MECHANISTIC UNDERSTANDING OF THE IMPACTS OF PATHOGENS ON HONEY BEE POLLINATOR HEALTH AND DEVELOP BIOLOGICALLY-BASED STRATEGIES TO COMBAT INFECTIONS WITH A LONG-TERM GOAL OF MITIGATING POLLINATOR LOSSES.