UNSUSTAINABLE LOSSES OF MANAGED HONEY BEE (APIS MELLIFERA) COLONIES OCCUR ANNUALLY EACH WINTER IN THE UNITED STATES. THESE COLONY DEATHS ARE PRIMARILY DUE TO UNCONTROLLED INFECTIONS OF DEFORMED WING VIRUS (DWV), TRANSMITTED BY VARROA DESTRUCTOR MITES. DWV EXHIBITS CONSIDERABLE GENETIC DIVERSITY, WITH TWO MAIN MASTER VARIANTS (I.E. STRAINS), DWV-A AND DWVB. RECENT STUDIES SUGGEST THE PROPORTIONS OF THESE STRAINS IN US HONEY BEE POPULATIONS ARE SHIFTING, BUT IT IS UNKNOWN IF DIFFERENTIAL INTERACTIONS BETWEEN THESE VARIANTS AND THEIR HONEY BEE HOSTS RESULT IN VARIATION IN DISEASE OUTCOMES. HERE, I WILL INVESTIGATE HOW HONEY BEE MOLECULAR RESPONSES, SUCH AS THE EXPRESSION OF IMMUNITY GENES,AND DISEASE OUTCOMES, INCLUDING SYMPTOMS AND MORTALITY,ARE MODULATED BY THE GENOTYPE AND DIVERSITY OF DWV POPULATIONS. I HAVE COLLECTED MULTIPLE DISTINCT DWV POPULATIONS, INCLUDING PURE DWV-A AND DWV-B ISOLATES, POPULATIONS FROM MANAGED APIARIES, AND POPULATIONS FROM FERAL (UNMANAGED) BEES THAT HAVE PERSISTED IN ISOLATION FOR 18+ YEARS. I WILL INFECT HONEY BEES WITH THESE DIFFERENT DWV POPULATIONS, AND COMPARE DIFFERENCES IN DISEASE SEVERITY AND HOST IMMUNE RESPONSE THROUGH RNA SEQUENCING. TOP DIFFERENTIALLY EXPRESSED GENES ASSOCIATED WITH A SEVERE INFECTION WILL BE TARGETED IN RNA INTERFERENCE (RNAI) EXPERIMENTS TO ASSESS THEIR POTENTIAL AS POSSIBLE ANTIVIRAL THERAPEUTICS TO MITIGATE DISEASE SEVERITY. BY INTEGRATING DWV TITERS, HONEY BEE GENE EXPRESSION, AND MORTALITY DATA, THE RESULTS FROM THESE PROPOSED STUDIES WILL PROVIDE INSIGHTS INTO THE GENETIC MECHANISMS MEDIATING DWV-HONEY BEE INTERACTIONS, INFORM MONITORING AND DISEASE MANAGEMENT, AND PROVIDE INSIGHTS INTO VIRAL-HOST EVOLUTIONARY DYNAMICS.