{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:20:51Z","timestamp":1760059251191,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Minnesota Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>T lymphocytes infiltrate the CNS in response to murine cytomegalovirus (MCMV) infection and form a pool of long-lived brain tissue-resident memory T-cells (bTRMs), which display markers of residency (i.e., CD103, CD69, CD49a). However, the functional role of these bTRMs is still unknown. By 30 days postinfection, a latent viral brain infection was established, as indicated by absence of viral transcripts (IE1, E1, and gB) produced during productive infection. Following intracerebroventricular injection of either depleting \u03b1-CD8 Ab (clone YTS169.4) or \u03b1-CD103-sap (clone IT50) into the brain, 90\u201395% T-cell depletion was achieved. Using luciferase-expressing mice, we observed recommenced imaging signals indicative of de novo MCMV IE promoter activity in depleted animals. Surprisingly, using an explant assay, we efficiently recovered reactivatable, infectious virus from untreated, latent animals, but not from those depleted of bTRMs (viral recovery in explants was reduced from 100% to 50% by day 21). We identified Lgals3 (galectin 3), Gpnmb (glycoprotein nonmetastatic melanoma protein B) and Hmox1 (heme oxygenase 1) as genes that were most upregulated in bTRM-depleted groups. When bTRMs were depleted, there was transient expression of viral IE genes which resulted in antiviral microglia with a phagocytic, disease-associated (DAM) or neurodegenerative (MGnD) phenotype. These data provide new insights into the role of bTRMs in controlling both CNS reactivation and driving microglial phenotypes.<\/jats:p>","DOI":"10.3390\/ijms26115275","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T09:22:41Z","timestamp":1748596961000},"page":"5275","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["bTRM Control of Murine Cytomegalovirus CNS Reactivation"],"prefix":"10.3390","volume":"26","author":[{"given":"Priyanka","family":"Chauhan","sequence":"first","affiliation":[{"name":"Neurovirology Laboratory, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuxian","family":"Hu","sequence":"additional","affiliation":[{"name":"Neurovirology Laboratory, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen S.","family":"Sheng","sequence":"additional","affiliation":[{"name":"Neurovirology Laboratory, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sujata","family":"Prasad","sequence":"additional","affiliation":[{"name":"Neurovirology Laboratory, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1976-2035","authenticated-orcid":false,"given":"James R.","family":"Lokensgard","sequence":"additional","affiliation":[{"name":"Neurovirology Laboratory, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hu, S., Rotschafer, J.H., Lokensgard, J.R., and Cheeran, M.C. 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