{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T01:22:22Z","timestamp":1788225742412,"version":"build-2803163510"},"reference-count":57,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"1","license":[{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,2]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n<jats:p>Powassan virus (POWV; family Flaviviridae) is a tick-borne encephalitic virus endemic to Canada, the United States, and Russia. In the United States, POWV is transmitted by ixodid ticks, and transmission foci reflect the geographic range of these vectors, primarily <jats:italic>Ixodes scapularis<\/jats:italic>. Thus, northeastern and midwestern regions of the United States contain the highest human case burdens and prevalence of infected ticks. Notably, New York (NY) and Minnesota (MN) have a long history of POWV transmission to humans. Over time, genetic divergence has occurred in these regions, giving rise to distinct midwestern and northeastern clades. Despite the established circulation of POWV, increases in reported human cases, and documented genetic distinction, an understanding of strain-specific POWV virulence is limited because of the lack of human isolates. In 2020 and 2021, two POWV strains were isolated from fatal human cases from MN (deer tick virus [DTV] MN-PV320) and NY (DTV NY21-027). Here, we provide the first characterization of geographically distinct, contemporary, human POWV isolates. Comprehensive genetic characterization was completed and phenotypic variability was determined in\u00a0vitro and in\u00a0vivo . Although strain fitness was similar in <jats:italic>I. scapularis<\/jats:italic>, higher mortality rates were measured in a susceptible POWV mouse model after infection with DTV NY21-027 compared with DTV MN-PV320. Genetic analysis revealed several variable amino acid substitutions, including I2173L in DTV NY21-027, which was selected for in all strains after neurological infection. These data suggest that genetic divergence of POWV strains from regionally distinct transmission foci could contribute to strain-dependent pathogenic potential in humans.<\/jats:p>","DOI":"10.4269\/ajtmh.24-0776","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T14:47:40Z","timestamp":1747147660000},"page":"106-116","source":"Crossref","is-referenced-by-count":4,"title":["Differential Virulence and Host-Specific Fitness of Regionally Distinct Human-Derived Powassan Virus Lineage 2 Strains"],"prefix":"10.4269","volume":"113","author":[{"given":"Rachel E.","family":"Lange","sequence":"first","affiliation":[{"name":"Arbovirus Laboratory, Wadsworth Center, New York State Department of Health, Slingerlands, New York;"},{"name":"Department of Biomedical Sciences, State University of New York University at Albany School of Public Health, Albany, New York;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia C.","family":"Pritchard","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota Twin Cities, St. Paul, Minnesota;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna S.","family":"Jaeger","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota Twin Cities, St. Paul, Minnesota;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler D.","family":"Bold","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Medicine, Department of Medicine, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"White","sequence":"additional","affiliation":[{"name":"Bureau of Communicable Disease Control, New York State Department of Health, Albany, New York;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy B.","family":"Dean","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Diseases, New York State Department of Health, Albany, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene C.","family":"Hull","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Diseases, New York State Department of Health, Albany, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"St. George","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, State University of New York University at Albany School of Public Health, Albany, New York;"},{"name":"Laboratory of Viral Diseases, New York State Department of Health, Albany, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan P.","family":"Dupuis","sequence":"additional","affiliation":[{"name":"Arbovirus Laboratory, Wadsworth Center, New York State Department of Health, Slingerlands, New York;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew T.","family":"Aliota","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota Twin Cities, St. Paul, Minnesota;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander T.","family":"Ciota","sequence":"additional","affiliation":[{"name":"Arbovirus Laboratory, Wadsworth Center, New York State Department of Health, Slingerlands, New York;"},{"name":"Department of Biomedical Sciences, State University of New York University at Albany School of Public Health, Albany, New York;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"b1","series-title":"Annu Rev Entomol","first-page":"95","article-title":"Update on Powassan virus: Emergence of a North American tick-borne 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