{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:43:28Z","timestamp":1790959408642,"version":"4.1.0"},"reference-count":74,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>West Nile Virus (WNV) can cause severe and long-lasting neurological disease and results in some neuropathology and neuroinflammation seen in Alzheimer\u2019s disease (AD). Exposure to WNV might impact AD-relevant behavioral and cognitive performance and neuropathology via AD-susceptibility genes (i.e., E4) and by inducing neuroinflammation (i.e., increases in TCR-\u03b1, IFN-\u03b3, TNF-\u03b1, and CXCL- 10). There are three human apolipoprotein E (E) isoforms, which play a role in cholesterol metabolism: E2, E3, and E4. Compared to E3, E4 is an AD risk factor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We crossed knock-in (KI) mice expressing human amyloid precursor protein (APP) containing the dominant NL-G-F mutations with human apoE targeted replacement (TR) mice and used middle-aged NL-G-F\/E3 and NL-G-F\/E4 mice to assess the role of prior WNV (subtype Kunjin virus) (KUNV) exposure on hAPP\/A\u03b2-induced behavioral alterations, cognitive injury, circadian body temperatures, viral loads, neuropathology, and transcript levels of four immune measures important in the detrimental effects of KUNV on brain function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>KUNV affected physiological, behavioral, cognitive, amyloid pathology, viral load, and immune measures in middle aged NL-G-F mice in an apoE isoform-dependent fashion. NL-G-F\/E4 mice were more susceptible to KUNV induced cognitive injury and prolonged viral load in the cortex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These results support an important apoE isoform-dependent role in modulating phenotypes in the NL-G-F AD mouse model following WNV exposure.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2025.1600119","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T05:29:55Z","timestamp":1750138195000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of West Nile virus on behavioral and cognitive performance, cortical A\u03b2 pathology, viral loads, and immune measures of middle-aged NL-G-F\/E3 and NL-G-F\/E4 mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Abigail","family":"O\u2019Niel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Parkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Pederson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Saltonstall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Bunnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ria","family":"Aggarwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phoebe","family":"Sandholm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kat","family":"Kessler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry F.","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica L.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alec J.","family":"Hirsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Raber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1038\/ijo.2016.93","article-title":"Metabolic shifts towards fatty acid usage and increased thermogenesis are associated with impaired adipogenesis in mice expressing human APOE4","volume":"40","author":"Arbones-Mainar","year":"2017","journal-title":"Int. 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