MANAGED HONEY BEE COLONIES ARE EXPERIENCING UNSUSTAINABLE ANNUAL LOSSES THAT ARE PARTLY DUE TOREDUCED IMMUNOCOMPETENCE THAT LEADS TO ACUTE VIRAL OUTBREAKS AND MORTALITY. TO HELP RESTOREHONEY BEE HEALTH DESPITE THE MYRIAD OF ENVIRONMENTAL STRESSORS, WE HAVE FOCUSED ONIDENTIFYING NOVEL PHYSIOLOGICAL PATHWAYS THAT CAN MITIGATE VIRUS-MEDIATED MORTALITY THROUGHINCREASED IMMUNE FUNCTION. WE PREVIOUSLY DEMONSTRATED THAT A FAMILY OF POTASSIUM IONCHANNELS, TERMED KATP CHANNELS, MEDIATE THE SURVIVAL OF HONEY BEES DURING INFECTION FROMISRAELI ACUTE PARALYSIS VIRUS (IAPV), SUGGESTING KATP CHANNELS MAY DRIVE ANTIVIRALIMMUNITY. INTERESTINGLY, THESE CHANNELS HAVE BEEN LINKED TO REGULATION OF REACTIVEOXYGEN SPECIES (ROS), WHICH ARE KNOWN TO FUNCTION AS AN IMMUNE SYSTEM STIMULATOR DURINGVIRUS INFECTION. THEREFORE, THE OVERARCHING GOALS OF THIS PROPOSAL IS TO BUILD A FUNCTIONALMODEL CHARACTERIZING THE RELATIONSHIP BETWEEN KATP CHANNELS, ROS, AND ANTIVIRALIMMUNITY IN BEES AND TO DETERMINE THE TOXICOLOGICAL RELEVANCE OF THIS PATHWAY. TOACHIEVE THIS GOAL, WE WILL COMPLETE THE FOLLOWING OBJECTIVES: 1) DETERMINE THE ABILITY OF KATPCHANNEL MODULATORS TO REDUCE MORTALITY STEMMING FROM DEFORMED WING VIRUS; 2) DETERMINE IFKATP CHANNELS REGULATE ROS TO CONTROL ANTIVIRAL IMMUNITY; AND 3) TEST THE HYPOTHESIS THATKATP MODULATORS WILL REDUCE VIRUS PREVALENCE AT THE LEVEL OF THE COLONY. FINDINGSWILL PROVIDE A FUNDAMENTAL UNDERSTANDING OF BEE IMMUNITY AND WILL REVEAL APPROACHESOR THE DEVELOPMENT OF NOVEL ANTIVIRAL THERAPEUTICS TO ADDRESS STAKEHOLDER NEEDS.