** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** THRIPS-TRANSMITTED TOMATO SPOTTED WILT VIRUS (TSWV) IS ONE OF THE TOP 10 MOST ECONOMICALLY IMPORTANT PLANT VIRUSES IN THE WORLD. THE DEPLOYMENT OF TOMATO CULTIVARS WITH SW-5 GENE THAT CONFERS BROAD-SPECTRUM RESISTANCE TO TSWV HAS BEEN VERY EFFECTIVE FOR REDUCING THE IMPACT OF TSWV. HOWEVER, THIS MANAGEMENT TACTIC IS BEING COMPROMISED DUE THE EMERGENCE OF RESISTANCE BREAKING (RB) STRAINS OF TSWV IN THE US AND GLOBALLY. AN INTEGRATIVE ANALYSES OF RB STRAIN PROTEIN INTERACTORS IN TOMATO GENOTYPES WITH SW-5 WILL BE USED TO GAIN INSIGHTS INTO THE RB STRAINS-HOST INTERACTOME. WE PROPOSE TO (1) MECHANISTICALLY UNDERSTAND THE BIOLOGY OF THESE INTERACTIONS AND THE HOST FACTORS THAT EITHER POSITIVELY OR NEGATIVELY REGULATE VIRAL REPLICATION AND PATHOGENESIS; (2) IDENTIFY HOST PROTEINS THAT ELICIT THE PLANT IMMUNE RESPONSE OR THAT CONFER RESISTANCE AGAINST VIRAL INFECTION; AND (3) IDENTIFY THE PLANT PROTEINS THAT COULD PLAY A ROLE IN THE VIRAL INFECTION AND ACCUMULATION, AS THESE PROTEINS COULD BE POTENTIAL TARGETS FOR ENGINEERING TSWV RESISTANCE. OUR PROPOSED WORK INTEGRATES MOLECULAR, GENETIC, PROTEOMIC AND METABOLOMIC APPROACHES TO SYSTEMATICALLY INVESTIGATE THE POTENTIAL MECHANISMS AND PATHWAYS RESPONSIBLE FOR TSWV INFECTION, INTERACTIONS WITH HOSTS AND THE UNDERLYING INTERACTIONS BETWEEN THE HOST AND RB STRAINS. THE OUTCOMES OF THIS RESEARCH WILL ILLUSTRATE THE MECHANISM BY WHICH PLANTS RESPOND AND DEFEND THEMSELVES DURING VIRAL INFECTION AND PATHOGENESIS. ADDITIONALLY, THIS RESEARCH WILL HELP DELINEATE THE MOLECULAR EVENTS THAT OCCUR DURING DIFFERENT STAGES OF VIRUS INFECTION AND PROVIDE INSIGHTS INTO HOW TSWV RB STRAINS POTENTIALLY OVERCOME THE HOST RESISTANCE.