**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** TOMATO SPOTTED WILT VIRUS (TSWV) AND RELATED THRIPS-BORNE ORTHOTOSPOVIRUSES ARE SOME OF THE BIGGEST THREATS TO PRODUCTION OF FOOD AND ORNAMENTAL CROPS. ORTHOTOSPOVIRUSES HAVE THE CAPACITY FOR RAPID GENETIC CHANGE LEADING TO THE EMERGENCE OF STRAINS WITH NEW BIOLOGICAL TRAITS. NEW SPECIES AND STRAINS OF ORTHOTOSPOVIRUS ARE CAUSING SIGNIFICANT YIELD LOSSES IN THE U.S.THE MOST EFFICIENT VECTOR OF TSWV, FRANKLINIELLA OCCIDENTALIS, IS KNOWN AS A SUPERVECTOR DUE TO ITS BROAD HOST RANGE AND CAPACITY TO TRANSMIT VIRUSES ACROSS DIVERSE LANDSCAPES. CONTROL OF F. OCCIDENTALIS IS CHALLENGING DUE TO THE BEHAVIOR OF THE INSECT AND THE ABILITY TO DEVELOP RESISTANCE TO INSECTICIDES. TSWV IS TRANSMITTED IN A CIRCULATIVE - PROPAGATIVE MANNER, I.E., THE VIRUS ENTERS THE BODY (GUT-ENTRY), REPLICATES AND DISSEMINATES TO INSECT TISSUE SYSTEMS, AND PERSISTS OVER THE LIFESPAN OF THE VECTOR. IN THIS CONTEXT, THRIPS AND PLANTS ARE HOSTS, AND WE ASSERT THAT EITHER OF THESE VIRUS-HOST INTERACTIONS CAN BE TARGETED TO DISRUPT THE INFECTION CYCLE.WE HAVE USED A SYSTEMS-BIOLOGY APPROACH TO IDENTIFY THRIPS PROTEINS OF F. OCCIDENTALIS THAT INTERACT DIRECTLY WITH TSWV VIRAL STRUCTURAL PROTEINS THAT PLAY ROLES IN VIRAL ATTACHMENT TO THRIPS GUT CELLS, VIRION STRUCTURE AND REPLICATION. BASED ON PROTEIN IDENTIFICATION AND PRELIMINARY EXPERIMENTATION, WE PRIORITIZED FOUR TSWV-INTERACTING PROTEINS (TIPS) TO PURSUE FUNCTIONALLY IN THIS PROJECT. WE RECENTLY DISCOVERED THAT TWO OF THESE TIPS RESPOND TO TSWV INFECTION IN YOUNG LARVAL THRIPS GUTS - THE GATEWAY TO VIRUS ENTRY, REPLICATION AND SUBSEQUENT TRANSMISSION BY ADULT THRIPS TO PLANTS. OUR ANALYSIS OF GENE NETWORKS ASSOCIATED WITH LARVAL GUTS POSITIONED THE TWO TIPS AS THE TWO MOST TIGHTLY CONNECTED GENES WITH OTHER TSWV-RESPONSIVE GENES. THESE TIGHT CONNECTIONS PROVIDE CLUES AND RESEARCH OPPORTUNITIES (THIS PROJECT) FOR DETERMINING THE ROLES OF THESE THRIPS PROTEINS IN THE VIRUS INFECTION PROCESS AND INSECT GROWTH AND DEVELOPMENT. THE EXPECTED OUTCOMES OF THIS PROJECT WILL ENABLE THE DEVELOPMENT OF NEW WAYS TO DISRUPT THE INTERACTION BETWEEN PLANT VIRUS AND INSECT VECTOR, AND THUS DIMINISH EPIDEMICS CAUSED BY OTHOTOSPOVIRUSES IN AGRICULTURAL PRODUCTION SYSTEMS.