{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:01:27Z","timestamp":1792684887067,"version":"4.5.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Neurological complications are increasingly recognized as a significant consequence of COVID-19; however, time-resolved, brain-specific characterization of transcriptional alterations underlying SARS-CoV-2\u2013associated neuroinflammation and neuronal injury remain limited. We hypothesized that brain transcriptional responses evolve dynamically during acute SARS-CoV-2 infection, resulting in temporal transcriptional programs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>KRT18-hACE2 transgenic mice were intranasally inoculated with SARS-CoV-2. Brain was harvested at 4 and 6 days post-infection (dpi) for analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Immunohistochemical analyses confirmed a broad spectrum of viral neurotropism and gliotropism, accompanied by an increased apoptotic burden, particularly in cortical neurons (ClCas3\/SATB2+). Robust activation of myeloid cells (Iba1+\/CD68+) provided evidence of neuroinflammation. Cytokine\/chemokine profiling demonstrated pronounced upregulation of inflammatory mediators (CXCL10, IL-12p40, CCL12), alongside reduced CX3CL1, suggesting impaired neuron\u2013microglia communication. Whole-transcriptome and gene ontology analyses uncovered stage-dependent molecular programs, with early alterations at 4 dpi enriched in protein ubiquitination, vesicle trafficking, and synaptic processes, followed by intensified innate immune activation and engagement of chromosomal maintenance pathways at 6 dpi. In parallel, pronounced suppression of mitochondrial function at 6 dpi, pointing to energy exhaustion and transcriptional-translational discordance, as supported by digital PCR and a substantial reduction in COXIV protein levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings provide a time-resolved molecular landscape of SARS-CoV-2\u2013induced neuroinflammation and metabolic stress, highlighting CNS vulnerability during severe infection and suggesting pathways potentially relevant to COVID-19-associated sequelae.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1716597","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T06:32:05Z","timestamp":1770013925000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Neuroinflammatory and transcriptional dynamics during SARS-CoV-2 infection in KRT18-hACE2 mouse brain"],"prefix":"10.3389","volume":"17","author":[{"given":"Dae-Gyun","family":"Ahn","sequence":"first","affiliation":[{"name":"Department of Convergent Research of Emerging Virus Infection, Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nhu Thi Quynh","family":"Mai","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Yeungnam University","place":["Gyeongsan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da-Jin","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Yeungnam University","place":["Gyeongsan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byoung-San","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Yeungnam University","place":["Gyeongsan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2020","journal-title":"nature"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2001017","article-title":"A novel coronavirus from patients with pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"New Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2022.02.006","article-title":"The neuroinvasiveness, neurotropism, and 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