{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T18:29:36Z","timestamp":1787941776085,"version":"build-2784847793"},"reference-count":41,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T00:00:00Z","timestamp":1729641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Powassan virus (POWV) is an emerging tick-borne virus that causes severe meningoencephalitis in the United States, Canada, and Russia. Serology is generally the preferred diagnostic modality, but PCR on cerebrospinal fluid, blood, or urine has an important role, particularly in immunocompromised patients who are unable to mount a serologic response. Although the perceived poor sensitivity of PCR in the general population may be due to the biology of infection and health-seeking behavior (with short viremic periods that end before hospital presentation), limitations in assay design may also contribute. Genome sequences from clinical POWV cases are extremely scarce; PCR assay design has been informed by those available, but the numbers are limited. Larger numbers of genome sequences from tick-derived POWV are available, but it is not known if POWV genomes from human infections broadly mirror genomes from tick hosts, or if human infections are caused by a subset of more virulent strains. We obtained viral genomic data from 10 previously unpublished POWV human infections and showed that they broadly mirror the diversity of genome sequences seen in ticks, including all three major clades (lineage I, lineage II Northeast, and lineage II Midwest). These newly published clinical POWV genome sequences include the first confirmed lineage I infection in the United States, highlighting the relevance of all clades in human disease. An in silico analysis of published POWV PCR assays shows that many assays were optimized against a single clade and have mismatches that may affect their sensitivity when applied across clades. This analysis serves as a launching point for improved PCR design for clinical diagnostics and environmental surveillance.<\/jats:p>","DOI":"10.3390\/v16111653","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T06:00:52Z","timestamp":1729663252000},"page":"1653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Analysis of Powassan Virus Genome Sequences from Human Cases Reveals Substantial Genetic Diversity with Implications for Molecular Assay Development"],"prefix":"10.3390","volume":"16","author":[{"given":"Erik H.","family":"Klontz","sequence":"first","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5372-0229","authenticated-orcid":false,"given":"Navid","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8764-0507","authenticated-orcid":false,"given":"Nolan","family":"Holbrook","sequence":"additional","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3432-0902","authenticated-orcid":false,"given":"Isaac H.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"3rd","given":"Sam R.","family":"Telford","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Global Health, Tufts University, North Grafton, MA 02155, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6902-9149","authenticated-orcid":false,"given":"Matthew T.","family":"Aliota","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota, Twin Cities, St. Paul, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0027-6480","authenticated-orcid":false,"given":"Chantal B. F.","family":"Vogels","sequence":"additional","affiliation":[{"name":"Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan D.","family":"Grubaugh","sequence":"additional","affiliation":[{"name":"Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Helgager","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53726, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly R.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention, Fort Collins, CO 80521, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1853-4222","authenticated-orcid":false,"given":"Jason","family":"Velez","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention, Fort Collins, CO 80521, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5942-1534","authenticated-orcid":false,"given":"Anne","family":"Piantadosi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles Y.","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Lemieux","sequence":"additional","affiliation":[{"name":"Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Branda","sequence":"additional","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.idc.2022.03.003","article-title":"Powassan Virus Encephalitis","volume":"36","author":"Piantadosi","year":"2022","journal-title":"Infect. 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