{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T01:22:20Z","timestamp":1788225740412,"version":"build-2803163510"},"reference-count":54,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:00:00Z","timestamp":1666310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Center for Advancing Translational Sciences","award":["UL1TR000071"],"award-info":[{"award-number":["UL1TR000071"]}]},{"name":"National Center for Advancing Translational Sciences","award":["NIEHS-T32ES007254"],"award-info":[{"award-number":["NIEHS-T32ES007254"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Powassan virus (POWV) is a tick-borne flavivirus (TBFV) that can cause severe encephalitis in humans with a case\u2013fatality rate as high as 11%. Patients who survive severe encephalitic disease can develop long-term neurological sequelae that can be debilitating and life-long. In this study, we have sought to characterize a primary human fetal brain neural stem cell system (hNSC), which can be differentiated into neuron and astrocyte co-cultures, to serve as a translational in vitro system for infection with POWV and a comparative mosquito-borne flavivirus (MBFV), West Nile virus (WNV). We found that both viruses are able to infect both cell types in the co-culture and that WNV elicits a strong inflammatory response characterized by increased cytokines IL-4, IL-6, IL-8, TNF-\u03b1 and IL-1\u03b2 and activation of apoptosis pathways. POWV infection resulted in fewer cytokine responses, as well as less detectable apoptosis, while neurons infected with POWV exhibited structural aberrations forming in the dendrites. These anomalies are consistent with previous findings in which tick-borne encephalitis virus (TBEV) infected murine primary neurons formed laminal membrane structures (LMS). Furthermore, these structural aberrations are also recapitulated in brain tissue from infected mice. Our findings indicate that POWV is capable of infecting human primary neurons and astrocytes without causing apparent widespread apoptosis, while forming punctate structures reminiscent with LMS in primary human neurons and in vivo.<\/jats:p>","DOI":"10.3390\/pathogens11101218","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T08:19:06Z","timestamp":1666599546000},"page":"1218","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Powassan Virus Induces Structural Changes in Human Neuronal Cells In Vitro and Murine Neurons In Vivo"],"prefix":"10.3390","volume":"11","author":[{"given":"Jacob","family":"Nelson","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9880-1900","authenticated-orcid":false,"given":"Lorenzo","family":"Ochoa","sequence":"additional","affiliation":[{"name":"Biomedical Engineering and Imaging Sciences Group, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Department of Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8320-7271","authenticated-orcid":false,"given":"Paula","family":"Villareal","sequence":"additional","affiliation":[{"name":"Biomedical Engineering and Imaging Sciences Group, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Dunn","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gracie","family":"Vargas","sequence":"additional","affiliation":[{"name":"Biomedical Engineering and Imaging Sciences Group, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Department of Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.wem.2021.01.005","article-title":"Underrecognized Tickborne Illnesses: Borrelia Miyamotoi and Powassan Virus","volume":"32","author":"Duke","year":"2021","journal-title":"Wilderness Environ. 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