Project Grant R01AI179758

POWASSAN VIRUS EVOLUTION, FITNESS, AND PATHOGENESIS IN THE NORTHEAST AND MIDWEST UNITED STATES - PROJECT SUMMARY TICK-BORNE POWASSAN VIRUS (POWV) IS AN EMERGING PUBLIC HEALTH THREAT, BUT HAS BEEN UNDERSTUDIED TO DATE. SINCE ITS DISCOVERY IN 1958, HUMAN CASES OF POWV HAVE BEEN REPORTED IN THE UNITED STATES, CANADA, AND RUSSIA. STARTING IN 2006, CONFIRMED CASES OF POWV HAVE INCREASED IN BOTH FREQUENCY AND SCOPE IN NEW ENGLAND AND THE UPPER MIDWEST. NOTABLY, POWV IS NOW CONSIDERED AN EMERGING PUBLIC HEALTH THREAT BECAUSE IT HAS BEEN FREQUENTLY ASSOCIATED WITH THE AGGRESSIVE, HUMAN-BITING BLACKLEGGED TICK VECTOR, IXODES SCAPU- LARIS. THE FUTURE SPREAD OF POWV IS UNPREDICTABLE, BUT IT WILL BE IMPORTANT TO UNDERSTAND THE POTENTIAL FOR MORE WIDESPREAD EMERGENCE. THE GOALS OF THIS PROJECT ARE TO EVALUATE WHETHER THERE ARE REGIONAL, LOCAL, AND EVEN HYPERLOCAL DIFFERENCES IN THE GENETIC STRUCTURE OF TICK AND POWV POPULATIONS THAT AFFECT PATTERNS OF POWV HOST/VECTOR COMPETENCE, VIRULENCE, AND EVOLUTION. THESE QUESTIONS ARE IMPORTANT BECAUSE OUR KNOWLEDGE OF HOW TICK-BORNE FLAVIVIRUSES ARE MAINTAINED IN DISTINCT TRANSMISSION FOCI AND HOW NEW TRANSMISSION FOCI EMERGE IS LIMITED. ACCORDINGLY, THROUGH THIS NIH/NIAID R01, WE WILL SEEK TO EXAMINE THESE RELATIONSHIPS ACROSS MINNE- SOTA AND NEW YORK, TWO STATES WITH INCREASING BURDENS OF TICK-BORNE DISEASE RISK. THERE ARE 3 SPECIFIC AIMS: 1. ASSESS THE DISTRIBUTION AND GENETIC STRUCTURE OF POWV AND IXODES SCAPULARIS FROM DISTINCT FOCI IN THE NORTHEAST (NY) AND MIDWEST (MN) U.S. 2. EVALUATE THE EXTENT TO WHICH TICK POPULATION INTERACTS WITH VIRAL GENOTYPE TO DRIVE LOCAL ADAPTA- TION AND REGIONAL VARIABILITY IN IXODES SCAPULARIS COMPETENCE FOR POWV. 3. DETERMINE HOW POWV GENETIC VARIABILITY AND REGIONAL SELECTIVE PRESSURES IMPACT HOST COMPE- TENCE AND DISEASE HETEROGENEITY. IN THESE STUDIES, WE WILL EXPAND POWV SURVEILLANCE ACTIVITIES IN MN TO INTENSELY SAMPLE POWV GENOMES AND TICK POPULATIONS FROM ACROSS THE STATE. THE NY STATE DEPARTMENT OF HEALTH HAS A ROBUST POWV SURVEILLANCE PROGRAM IN PLACE FOR THIS PROJECT THAT WE WILL LEVERAGE. WE WILL ALSO SEEK TO UNDERSTAND THE PHENOTYPIC AND GE- NOTYPIC UNDERPINNINGS OF VIRUS-HOST DYNAMICS FOR POWV USING MOUSE AND TICK EXPERIMENTAL SYSTEMS. THESE STUDIES ARE CRITICALLY IMPORTANT BECAUSE POWV LIKELY WILL CONTINUE TO EMERGE IN THE FUTURE. THEREFORE, UNDER- STANDING HOW POWV OVERCOMES EVOLUTIONARY BARRIERS TO EMERGE AND CAUSE DISEASE IN HUMANS WILL BE CRITICAL FOR PREDICTION, PREVENTION, AND CONTROL OF THIS ARBOVIRAL DISEASE.