{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:22:11Z","timestamp":1790824931836,"version":"4.1.0"},"reference-count":134,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI179817, RO1AI183762, R21AI180288"],"award-info":[{"award-number":["R01AI179817, RO1AI183762, R21AI180288"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"name":"U.S. Department of Defense","award":["W81XWH2210702"],"award-info":[{"award-number":["W81XWH2210702"]}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R61AI179732, R01AI152208"],"award-info":[{"award-number":["R61AI179732, R01AI152208"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"name":"U.S. Department of Defense","award":["HT94252410378"],"award-info":[{"award-number":["HT94252410378"]}]},{"DOI":"10.13039\/501100000156","name":"Fonds de Recherche du Qu\u00e9bec - Sant\u00e9","doi-asserted-by":"crossref","award":["330358"],"award-info":[{"award-number":["330358"]}],"id":[{"id":"10.13039\/501100000156","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000156","name":"Fonds de Recherche du Qu\u00e9bec - Sant\u00e9","doi-asserted-by":"crossref","award":["370123"],"award-info":[{"award-number":["370123"]}],"id":[{"id":"10.13039\/501100000156","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R21AI171578, R21AI83259, R21AI96576"],"award-info":[{"award-number":["R21AI171578, R21AI83259, R21AI96576"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,8,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Powassan virus (POWV) causes lethal encephalitis in the elderly and long-term neurological sequelae in survivors. Mirroring human disease, POWV strain LI9 directs age-dependent lethality in C57BL\/6 (B6) mice, resulting in spongiform encephalitis, gliosis, and inflammatory cytokine\/chemokine responses in the CNS. However, the mechanisms underlying age-dependent lethality and persistent neurodegenerative disease in POWV survivors remain to be resolved. Here, we analyzed cellular CNS responses to POWV LI9 infection in young (10-week-old) and aged (50-week-old) mice using single-cell RNA sequencing. Infection of young mice resulted in inflammatory CNS infiltrates (NK, CD4\/CD8 T cells, and monocytes) and interferon responses that coincide with peak viral burden. In contrast, the CNS of aged infected mice instead featured upregulated astrocyte and neuronal genes associated with neurodegenerative and Alzheimer\u2019s disease pathways and the transition of homeostatic microglia to a Trem2\u2013ApoE-linked disease-associated microglial transcriptional state. Histological analysis revealed that amyloid precursor protein (APP)\/amyloid-\u03b2 (A\u03b2) accumulated in the CNS following POWV infection and that POWV envelope protein and APP\/A\u03b2 were selectively localized within layers L5\/L6 of the cerebral cortex. POWV kinetically increased perinuclear APP\/A\u03b2 accumulation during acute infection and was highly expressed in the CNS of POWV survivors. Our findings reveal that POWV triggers glial cell responses and a neurodegenerative disease-associated microglia program of Alzheimer\u2019s-like APP\/A\u03b2 accumulation in mice, which is consistent with long-term neurological sequelae in human POWV survivors.<\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>Powassan virus (POWV) causes lethal encephalitis and long-term cognitive deficits in survivors. Using an age-dependent murine model, we reveal that POWV-infected young mice direct robust CNS inflammatory infiltrates associated with viral clearance, whereas aged mice exhibit impaired immune responses and a shift from homeostatic to neurodegenerative glial cell states. POWV prompted the induction of disease-associated microglia (DAM) and Trem2\u2013ApoE axis transcriptional responses that are hallmarks of APP\/amyloid-\u03b2 (A\u03b2) accumulation in Alzheimer\u2019s disease (AD). Remarkably, POWV induced progressive APP\/A\u03b2 accumulation in young and aged mice that persisted in survivors after viral clearance. This suggests that POWV induces an APP\/A\u03b2 neurodegenerative process and provides a potential cause of long-term neurological sequelae observed in human POWV survivors. Our data suggest that POWV initiates or exacerbates AD-like neuropathology and further rationalizes investigating the role of APP\/A\u03b2 responses in other encephalitic viruses.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01294-26","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T15:16:36Z","timestamp":1784042196000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Single-cell analysis of Powassan virus-infected brains reveals age-dependent neuroinflammatory crosstalk and progressive Alzheimer\u2019s-like APP\/A\u03b2 accumulation"],"prefix":"10.1128","volume":"17","author":[{"given":"Marcos Romario Matos","family":"de Souza","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05qghxh33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Center for Infectious Disease, Renaissance School of Medicine, Stony Brook University","place":["Stony Brook, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa R.","family":"Lindner","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05qghxh33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Center for Infectious Disease, Renaissance School of Medicine, Stony Brook University","place":["Stony Brook, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Mladinich-Valenti","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02rrhsz92","id-type":"ROR","asserted-by":"publisher"}],"name":"SUNY Old Westbury","place":["Old Westbury, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena E.","family":"Gorbunova","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05qghxh33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Center for Infectious Disease, Renaissance School of Medicine, Stony Brook University","place":["Stony Brook, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varvara","family":"Kirillov","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05qghxh33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Center for Infectious Disease, Renaissance School of Medicine, Stony Brook University","place":["Stony Brook, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisling G.","family":"Byrne","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05qghxh33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Center for Infectious 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P.","family":"Gomes","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Scientifique, Centre Armand-Frappier Sant\u00e9 Biotechnologie","place":["Quebec, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7390-8250","authenticated-orcid":true,"given":"Laurent","family":"Chatel-Chaix","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Scientifique, Centre Armand-Frappier Sant\u00e9 Biotechnologie","place":["Quebec, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2095-9705","authenticated-orcid":true,"given":"Hwan Keun","family":"Kim","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05qghxh33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Center for Infectious Disease, Renaissance School of Medicine, Stony Brook University","place":["Stony Brook, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9156-1222","authenticated-orcid":true,"given":"Erich R.","family":"Mackow","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05qghxh33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Center for Infectious Disease, Renaissance School of Medicine, Stony Brook University","place":["Stony Brook, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00106-17"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofaa392"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-020-0714-0"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1183"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2004.71.3.0700268"},{"key":"e_1_3_6_7_2","first-page":"708","article-title":"Powassan virus: isolation of virus from a fatal case of encephalitis","volume":"80","author":"McLean DM","year":"1959","unstructured":"McLean DM, Donohue WL. 1959. 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