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Infections can induce a range of acute, subacute, and progressing brain disease, and in recent years it has emerged that immune responses are involved in the pathogenesis of these diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mice were infected with HSV-1 through corneal infection, and the brain stem was analyzed using single-cell and GeoMx spatial transcriptomics. Through these technologies we profiled temporal transcriptomic changes in cell populations, pathways, and cell-cell communication associated with antiviral activity and inflammation-induced disturbance of physiological brain structures and activities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that microglia proportions increased early after HSV-1 infection, followed by monocyte influx and later by T cells. The blood-brain barrier was disrupted, and transcriptomic profiles associated with homeostatic brain transcriptional activities were altered. Early transcriptional responses were dominated by antiviral and inflammatory activities. A microglia subpopulation with high type I interferon and chemokine expression localized to infection sites, likely mediating antiviral defense and immune recruitment. Monocyte subpopulations displayed a broader activation profile than microglia and was a central mediator of crosstalk between immune cells. Cytokines from microglia, monocytes, and T cells reprogrammed brain cells, notably endothelial cells and oligodendrocytes, disrupting brain functions. Comparing datasets from various brain diseases revealed the identified microglia subpopulation as specific to viral infections.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study identifies a unique population of virus-activated microglia with antiviral and proinflammatory properties and reveals monocytes to be a key driver of interactions driving pathology in the virus-infected brain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12974-025-03471-x","type":"journal-article","created":{"date-parts":[[2025,5,31]],"date-time":"2025-05-31T04:42:42Z","timestamp":1748666562000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Temporally resolved single-cell RNA sequencing reveals protective and pathological responses during herpes simplex virus CNS infection"],"prefix":"10.1186","volume":"22","author":[{"given":"Xiangning","family":"Ding","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida H.","family":"Klaestrup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara R. 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