{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:10:55Z","timestamp":1788844255674,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["#T32AI007526-23"],"award-info":[{"award-number":["#T32AI007526-23"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"award":["#T32AI007526-23"],"award-info":[{"award-number":["#T32AI007526-23"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"name":"UTMB Health Institute for Human Infections and Immunity"},{"name":"NIH","award":["1U19AI181960-01"],"award-info":[{"award-number":["1U19AI181960-01"]}]},{"award":["1U19AI181960-01"],"award-info":[{"award-number":["1U19AI181960-01"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Powassan virus (POWV) is an emerging tick-borne orthoflavivirus with consistently increasing annual prevalence. Though understood as a vector-transmitted virus associated with neurological disease, a 2016 fatal case of an immunocompromised 63-year-old man reported testicular pain with postmortem detection of viral antigen in the testes, suggesting an altered tropism. The extent to which POWV can infect testes remains unclear. We used a BALB\/c mouse model of POWV to elucidate the potential of POWV to establish infection in testes and model a potential mechanism of testicular tropism. Here, we report that POWV productively infects the male reproductive tract of mice. We find that POWV consistently infects mouse testes and epididymides at 3 and 5 days post-infection (dpi) with peak titers measuring 6.1 log10 PFU\/gram of tissue in testes. Furthermore, we find that at 5 dpi, POWV-infected mice testes are significantly higher in mass than uninfected controls. Due to macrophages being implicated in driving testicular pathogenesis in Zika virus, a related orthoflavivirus, we depleted phagocytic cells using clodronate liposomes prior to POWV infection and compared them to control liposome-treated mice. Depletion of phagocytic cells was associated with higher and sustained viremia and significantly higher viral organ burden in the male reproductive tract of mice. Gene expression analysis revealed a robust antiviral, inflammatory, and chemokine response in the testes that was further amplified following phagocytic-cell depletion. These findings implicate the male reproductive tract as a previously underrecognized target of POWV disease and identify phagocytic cells as key in limiting viral infection of testes in mice.<\/jats:p>","DOI":"10.3390\/v18090979","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T16:30:02Z","timestamp":1788798602000},"page":"979","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Powassan Virus Infects Mouse Testes and Reveals a Protective Role for Phagocytic Cells"],"prefix":"10.3390","volume":"18","author":[{"given":"E. Eldridge","family":"Hager-Soto","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Esteban","family":"Arroyave","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Eduardo","family":"Eyzaguirre","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Omar A.","family":"Saldarriaga","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8413-8960","authenticated-orcid":false,"given":"Alexander N.","family":"Freiberg","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2450-2374","authenticated-orcid":false,"given":"Shannan L.","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2523887","DOI":"10.1080\/21505594.2025.2523887","article-title":"Pathogenicity and Virulence of Powassan Virus","volume":"16","author":"Kaur","year":"2025","journal-title":"Virulence"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kakoullis, L., Vaz, V.R., Kaur, D., Kakoulli, S., Panos, G., Chen, L.H., and Behlau, I. 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