{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T02:33:04Z","timestamp":1788834784481,"version":"build-2803163510"},"reference-count":110,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T00:00:00Z","timestamp":1680566400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T00:00:00Z","timestamp":1680566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","award":["1088242"],"award-info":[{"award-number":["1088242"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["acta neuropathol commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>As the resident parenchymal myeloid population in the central nervous system (CNS), microglia are strategically positioned to respond to neurotropic virus invasion and have been implicated in promoting both disease resolution and progression in the acute and post-infectious phase of virus encephalitis. In a mouse model of West Nile virus encephalitis (WNE), infection of the CNS results in recruitment of large numbers of peripheral immune cells into the brain, the majority being nitric\u00a0oxide (NO)-producing Ly6C<jats:sup>hi<\/jats:sup> inflammatory monocyte-derived cells (MCs). In this model, these cells enhance immunopathology and mortality. However, the contribution of microglia to this response is currently undefined. Here we used a combination of experimental tools, including single-cell RNA sequencing (scRNA-seq), microglia and MC depletion reagents, high-dimensional spectral cytometry and computational algorithms to dissect the differential contribution of microglia and MCs to the anti-viral immune response in severe neuroinflammation seen in WNE. Intriguingly, analysis of scRNA-seq data revealed 6 unique microglia and 3 unique MC clusters that were predominantly timepoint-specific, demonstrating substantial transcriptional adaptation with disease progression over the course of WNE. While microglia and MC adopted unique gene expression profiles, gene ontology enrichment analysis, coupled with microglia and MC depletion studies, demonstrated a role for both of these cells in the trafficking of peripheral immune cells into the CNS, T cell responses and viral clearance. Over the course of infection, microglia transitioned from a homeostatic to an <jats:italic>anti-viral<\/jats:italic> and then into an <jats:italic>immune cell-recruiting<\/jats:italic> phenotype. Conversely, MC adopted <jats:italic>antigen-presenting<\/jats:italic>, <jats:italic>immune cell-recruiting<\/jats:italic> and <jats:italic>NO-producing<\/jats:italic> phenotypes, which all had anti-viral function. Overall, this study defines for the first time the single-cell transcriptomic responses of microglia and MCs over the course of WNE, demonstrating both protective and pathological roles of these cells that could potentially be targeted for differential therapeutic intervention to dampen immune-mediated pathology, while maintaining viral clearance functions.<\/jats:p>","DOI":"10.1186\/s40478-023-01547-4","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T00:39:17Z","timestamp":1680741557000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Temporal tracking of microglial and monocyte single-cell transcriptomics in lethal flavivirus infection"],"prefix":"10.1186","volume":"11","author":[{"given":"Alanna G.","family":"Spiteri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire L.","family":"Wishart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duan","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barney","family":"Viengkhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Macia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus J.","family":"Hofer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3877-9772","authenticated-orcid":false,"given":"Nicholas J. C.","family":"King","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,4,4]]},"reference":[{"key":"1547_CR1","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1007\/978-1-4939-9454-0_12","volume":"1989","author":"TM Ashhurst","year":"2019","unstructured":"Ashhurst TM, Cox DA, Smith AL, King NJC (2019) Analysis of the Murine bone marrow hematopoietic system using mass and flow cytometry. Methods Mol Biol 1989:159\u2013192. https:\/\/doi.org\/10.1007\/978-1-4939-9454-0_12","journal-title":"Methods Mol Biol"},{"key":"1547_CR2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens8040193","author":"F Bai","year":"2019","unstructured":"Bai F, Thompson EA, Vig PJS, Leis AA (2019) Current understanding of west Nile Virus clinical manifestations, immune responses, neuroinvasion, and immunotherapeutic implications. Pathogens. https:\/\/doi.org\/10.3390\/pathogens8040193","journal-title":"Pathogens"},{"key":"1547_CR3","doi-asserted-by":"publisher","first-page":"E1738","DOI":"10.1073\/pnas.1525528113","volume":"113","author":"ML Bennett","year":"2016","unstructured":"Bennett ML, Bennett FC, Liddelow SA, Ajami B, Zamanian JL, Fernhoff NB, Mulinyawe SB, Bohlen CJ, Adil A, Tucker A et al (2016) New tools for studying microglia in the mouse and human CNS. Proc Natl Acad Sci U S A 113:E1738-1746. https:\/\/doi.org\/10.1073\/pnas.1525528113","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1547_CR4","doi-asserted-by":"publisher","first-page":"e70","DOI":"10.1002\/cpim.70","volume":"125","author":"CJ Bohlen","year":"2019","unstructured":"Bohlen CJ, Bennett FC, Bennett ML (2019) Isolation and culture of microglia. Curr Protoc Immunol 125:e70. https:\/\/doi.org\/10.1002\/cpim.70","journal-title":"Curr Protoc Immunol"},{"key":"1547_CR5","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1016\/j.cell.2009.12.017","volume":"139","author":"AL Brass","year":"2009","unstructured":"Brass AL, Huang IC, Benita Y, John SP, Krishnan MN, Feeley EM, Ryan BJ, Weyer JL, van der Weyden L, Fikrig E et al (2009) The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell 139:1243\u20131254. https:\/\/doi.org\/10.1016\/j.cell.2009.12.017","journal-title":"Cell"},{"key":"1547_CR6","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s13040-019-0204-1","volume":"12","author":"A Brionne","year":"2019","unstructured":"Brionne A, Juanchich A, Hennequet-Antier C (2019) ViSEAGO: a Bioconductor package for clustering biological functions using Gene Ontology and semantic similarity. BioData Min 12:16. https:\/\/doi.org\/10.1186\/s13040-019-0204-1","journal-title":"BioData Min"},{"key":"1547_CR7","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.47117","author":"DG Brown","year":"2019","unstructured":"Brown DG, Soto R, Yandamuri S, Stone C, Dickey L, Gomes-Neto JC, Pastuzyn ED, Bell R, Petersen C, Buhrke K et al (2019) The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling. Elife. https:\/\/doi.org\/10.7554\/eLife.47117","journal-title":"Elife"},{"key":"1547_CR8","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/nbt.4096","volume":"36","author":"A Butler","year":"2018","unstructured":"Butler A, Hoffman P, Smibert P, Papalexi E, Satija R (2018) Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat Biotechnol 36:411\u2013420. https:\/\/doi.org\/10.1038\/nbt.4096","journal-title":"Nat Biotechnol"},{"key":"1547_CR9","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/nn.3599","volume":"17","author":"O Butovsky","year":"2014","unstructured":"Butovsky O, Jedrychowski MP, Moore CS, Cialic R, Lanser AJ, Gabriely G, Koeglsperger T, Dake B, Wu PM, Doykan CE et al (2014) Identification of a unique TGF-\u03b2-dependent molecular and functional signature in microglia. Nat Neurosci 17:131\u2013143. https:\/\/doi.org\/10.1038\/nn.3599","journal-title":"Nat Neurosci"},{"key":"1547_CR10","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1038\/s41586-019-0969-x","volume":"566","author":"J Cao","year":"2019","unstructured":"Cao J, Spielmann M, Qiu X, Huang X, Ibrahim DM, Hill AJ, Zhang F, Mundlos S, Christiansen L, Steemers FJ et al (2019) The single-cell transcriptional landscape of mammalian organogenesis. Nature 566:496\u2013502. https:\/\/doi.org\/10.1038\/s41586-019-0969-x","journal-title":"Nature"},{"key":"1547_CR11","unstructured":"Carlson M (2019) org.Mm.eg.db: Genome wide annotation for Mouse. R package version, City"},{"key":"1547_CR12","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1080\/13550280500384982","volume":"11","author":"MC Cheeran","year":"2005","unstructured":"Cheeran MC, Hu S, Sheng WS, Rashid A, Peterson PK, Lokensgard JR (2005) Differential responses of human brain cells to West Nile virus infection. J Neurovirol 11:512\u2013524. https:\/\/doi.org\/10.1080\/13550280500384982","journal-title":"J Neurovirol"},{"key":"1547_CR13","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.celrep.2018.09.003","volume":"25","author":"C Chhatbar","year":"2018","unstructured":"Chhatbar C, Detje CN, Grabski E, Borst K, Spanier J, Ghita L, Elliott DA, Jordao MJC, Mueller N, Sutton J et al (2018) Type I interferon receptor signaling of neurons and astrocytes regulates microglia activation during viral encephalitis. Cell Rep 25:118-129.e114. https:\/\/doi.org\/10.1016\/j.celrep.2018.09.003","journal-title":"Cell Rep"},{"key":"1547_CR14","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1016\/j.clinthera.2017.07.001","volume":"39","author":"MH Collins","year":"2017","unstructured":"Collins MH, Metz SW (2017) Progress and works in progress: update on flavivirus vaccine development. Clin Ther 39:1519\u20131536. https:\/\/doi.org\/10.1016\/j.clinthera.2017.07.001","journal-title":"Clin Ther"},{"key":"1547_CR15","doi-asserted-by":"publisher","first-page":"2938","DOI":"10.1093\/bioinformatics\/btx364","volume":"33","author":"JR Conway","year":"2017","unstructured":"Conway JR, Lex A, Gehlenborg N (2017) UpSetR: an R package for the visualization of intersecting sets and their properties. Bioinformatics 33:2938\u20132940","journal-title":"Bioinformatics"},{"key":"1547_CR16","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1186\/s12974-019-1545-x","volume":"16","author":"AB DePaula-Silva","year":"2019","unstructured":"DePaula-Silva AB, Gorbea C, Doty DJ, Libbey JE, Sanchez JMS, Hanak TJ, Cazalla D, Fujinami RS (2019) Differential transcriptional profiles identify microglial- and macrophage-specific gene markers expressed during virus-induced neuroinflammation. J Neuroinflamm 16:152. https:\/\/doi.org\/10.1186\/s12974-019-1545-x","journal-title":"J Neuroinflamm"},{"key":"1547_CR17","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1186\/s12974-021-02221-z","volume":"18","author":"W Enlow","year":"2021","unstructured":"Enlow W, Bordeleau M, Piret J, Ibanez FG, Uyar O, Venable MC, Goyette N, Carbonneau J, Tremblay ME, Boivin G (2021) Microglia are involved in phagocytosis and extracellular digestion during Zika virus encephalitis in young adult immunodeficient mice. J Neuroinflamm 18:178. https:\/\/doi.org\/10.1186\/s12974-021-02221-z","journal-title":"J Neuroinflamm"},{"key":"1547_CR18","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1007\/s00401-018-1885-0","volume":"136","author":"R Fekete","year":"2018","unstructured":"Fekete R, Cserep C, Lenart N, Toth K, Orsolits B, Martinecz B, Mehes E, Szabo B, Nemeth V, Gonci B et al (2018) Microglia control the spread of neurotropic virus infection via P2Y12 signalling and recruit monocytes through P2Y12-independent mechanisms. Acta Neuropathol 136:461\u2013482. https:\/\/doi.org\/10.1007\/s00401-018-1885-0","journal-title":"Acta Neuropathol"},{"key":"1547_CR19","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s12974-019-1397-4","volume":"16","author":"KE Funk","year":"2019","unstructured":"Funk KE, Klein RS (2019) CSF1R antagonism limits local restimulation of antiviral CD8+ T cells during viral encephalitis. J Neuroinflamm 16:22. https:\/\/doi.org\/10.1186\/s12974-019-1397-4","journal-title":"J Neuroinflamm"},{"key":"1547_CR20","doi-asserted-by":"publisher","first-page":"6585","DOI":"10.1007\/s00018-021-03916-5","volume":"78","author":"AM Galow","year":"2021","unstructured":"Galow AM, Kussauer S, Wolfien M, Brunner RM, Goldammer T, David R, Hoeflich A (2021) Quality control in scRNA-Seq can discriminate pacemaker cells: the mtRNA bias. Cell Mol Life Sci 78:6585\u20136592. https:\/\/doi.org\/10.1007\/s00018-021-03916-5","journal-title":"Cell Mol Life Sci"},{"key":"1547_CR21","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1038\/s41593-019-0427-y","volume":"22","author":"C Garber","year":"2019","unstructured":"Garber C, Soung A, Vollmer LL, Kanmogne M, Last A, Brown J, Klein RS (2019) T cells promote microglia-mediated synaptic elimination and cognitive dysfunction during recovery from neuropathogenic flaviviruses. Nat Neurosci 22:1276\u20131288. https:\/\/doi.org\/10.1038\/s41593-019-0427-y","journal-title":"Nat Neurosci"},{"key":"1547_CR22","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1111\/j.1471-4159.2007.04798.x","volume":"103","author":"DR Getts","year":"2007","unstructured":"Getts DR, Matsumoto I, M\u00fcller M, Getts MT, Radford J, Shrestha B, Campbell IL, King NJ (2007) Role of IFN-\u03b3 in an experimental murine model of West Nile virus-induced seizures. J Neurochem 103:1019\u20131030","journal-title":"J Neurochem"},{"key":"1547_CR23","doi-asserted-by":"publisher","first-page":"219ra217","DOI":"10.1126\/scitranslmed.3007563","volume":"6","author":"DR Getts","year":"2014","unstructured":"Getts DR, Terry RL, Getts MT, Deffrasnes C, M\u00fcller M, van Vreden C, Ashhurst TM, Chami B, McCarthy D, Wu H (2014) Therapeutic inflammatory monocyte modulation using immune-modifying microparticles. Sci Transl Med 6:219ra217","journal-title":"Sci Transl Med"},{"key":"1547_CR24","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1186\/1742-2094-9-246","volume":"9","author":"DR Getts","year":"2012","unstructured":"Getts DR, Terry RL, Getts MT, M\u00fcller M, Rana S, Deffrasnes C, Ashhurst TM, Radford J, Hofer M, Thomas S (2012) Targeted blockade in lethal West Nile virus encephalitis indicates a crucial role for very late antigen (VLA)-4-dependent recruitment of nitric oxide-producing macrophages. J Neuroinflamm 9:246","journal-title":"J Neuroinflamm"},{"key":"1547_CR25","doi-asserted-by":"publisher","first-page":"2319","DOI":"10.1084\/jem.20080421","volume":"205","author":"DR Getts","year":"2008","unstructured":"Getts DR, Terry RL, Getts MT, M\u00fcller M, Rana S, Shrestha B, Radford J, Van Rooijen N, Campbell IL, King NJC (2008) Ly6c+ \u201cinflammatory monocytes\u201d are microglial precursors recruited in a pathogenic manner in West Nile virus encephalitis. J Exp Med 205:2319\u20132337. https:\/\/doi.org\/10.1084\/jem.20080421","journal-title":"J Exp Med"},{"key":"1547_CR26","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1084\/jem.20042530","volume":"202","author":"WG Glass","year":"2005","unstructured":"Glass WG, Lim JK, Cholera R, Pletnev AG, Gao J-L, Murphy PM (2005) Chemokine receptor CCR5 promotes leukocyte trafficking to the brain and survival in West Nile virus infection. J Exp Med 202:1087\u20131098. https:\/\/doi.org\/10.1084\/jem.20042530","journal-title":"J Exp Med"},{"key":"1547_CR27","doi-asserted-by":"publisher","first-page":"726421","DOI":"10.3389\/fimmu.2021.726421","volume":"12","author":"EN Goddery","year":"2021","unstructured":"Goddery EN, Fain CE, Lipovsky CG, Ayasoufi K, Yokanovich LT, Malo CS, Khadka RH, Tritz ZP, Jin F, Hansen MJ et al (2021) Microglia and perivascular macrophages act as antigen presenting cells to promote CD8 T cell infiltration of the brain. Front Immunol 12:726421. https:\/\/doi.org\/10.3389\/fimmu.2021.726421","journal-title":"Front Immunol"},{"key":"1547_CR28","doi-asserted-by":"publisher","first-page":"8212","DOI":"10.1128\/JVI.00581-16","volume":"90","author":"MJ Gorman","year":"2016","unstructured":"Gorman MJ, Poddar S, Farzan M, Diamond MS (2016) The interferon-stimulated gene Ifitm3 restricts west nile virus infection and pathogenesis. J Virol 90:8212\u20138225. https:\/\/doi.org\/10.1128\/JVI.00581-16","journal-title":"J Virol"},{"key":"1547_CR29","doi-asserted-by":"publisher","DOI":"10.1126\/science.aal3222","author":"D Gosselin","year":"2017","unstructured":"Gosselin D, Skola D, Coufal NG, Holtman IR, Schlachetzki JCM, Sajti E, Jaeger BN, O\u2019Connor C, Fitzpatrick C, Pasillas MP et al (2017) An environment-dependent transcriptional network specifies human microglia identity. Science. https:\/\/doi.org\/10.1126\/science.aal3222","journal-title":"Science"},{"key":"1547_CR30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2019695118","author":"KN Green","year":"2021","unstructured":"Green KN, Hume DA (2021) On the utility of CSF1R inhibitors. Proc Natl Acad Sci USA. https:\/\/doi.org\/10.1073\/pnas.2019695118","journal-title":"Proc Natl Acad Sci USA"},{"key":"1547_CR31","doi-asserted-by":"publisher","first-page":"249","DOI":"10.3389\/fimmu.2015.00249","volume":"6","author":"M Greter","year":"2015","unstructured":"Greter M, Lelios I, Croxford AL (2015) Microglia versus myeloid cell nomenclature during brain inflammation. Front Immunol 6:249. https:\/\/doi.org\/10.3389\/fimmu.2015.00249","journal-title":"Front Immunol"},{"key":"1547_CR32","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21228603","author":"J Han","year":"2020","unstructured":"Han J, Fan Y, Zhou K, Zhu K, Blomgren K, Lund H, Zhang XM, Harris RA (2020) Underestimated peripheral effects following pharmacological and conditional genetic microglial depletion. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms21228603","journal-title":"Int J Mol Sci"},{"key":"1547_CR33","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","volume":"184","author":"Y Hao","year":"2021","unstructured":"Hao Y, Hao S, Andersen-Nissen E, Mauck WM 3rd, Zheng S, Butler A, Lee MJ, Wilk AJ, Darby C, Zager M et al (2021) Integrated analysis of multimodal single-cell data. Cell 184:3573-3587.e3529. https:\/\/doi.org\/10.1016\/j.cell.2021.04.048","journal-title":"Cell"},{"key":"1547_CR34","doi-asserted-by":"publisher","first-page":"4624","DOI":"10.1074\/jbc.M508649200","volume":"281","author":"A Kajaste-Rudnitski","year":"2006","unstructured":"Kajaste-Rudnitski A, Mashimo T, Frenkiel MP, Guenet JL, Lucas M, Despres P (2006) The 2\u2019,5\u2019-oligoadenylate synthetase 1b is a potent inhibitor of West Nile virus replication inside infected cells. J Biol Chem 281:4624\u20134637. https:\/\/doi.org\/10.1074\/jbc.M508649200","journal-title":"J Biol Chem"},{"key":"1547_CR35","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/sj.icb.7100012","volume":"85","author":"NJ King","year":"2007","unstructured":"King NJ, Getts DR, Getts MT, Rana S, Shrestha B, Kesson AM (2007) Immunopathology of flavivirus infections. Immunol Cell Biol 85:33\u201342. https:\/\/doi.org\/10.1038\/sj.icb.7100012","journal-title":"Immunol Cell Biol"},{"issue":"Pt 10","key":"1547_CR36","doi-asserted-by":"publisher","first-page":"2535","DOI":"10.1099\/0022-1317-69-10-2535","volume":"69","author":"NJ King","year":"1988","unstructured":"King NJ, Kesson AM (1988) Interferon-independent increases in class I major histocompatibility complex antigen expression follow flavivirus infection. J Gen Virol 69(Pt 10):2535\u20132543. https:\/\/doi.org\/10.1099\/0022-1317-69-10-2535","journal-title":"J Gen Virol"},{"key":"1547_CR37","volume-title":"The immunopathogenesis of neurotropic flavivirus infection","author":"NJC King","year":"2011","unstructured":"King NJC, Van Vreden C, Terry RL, Getts DR, Yeung AWS, Teague-Getts M, Davison AM, Deffrasnes C, Munoz-Erazo L (2011) The immunopathogenesis of neurotropic flavivirus infection. InTech"},{"key":"1547_CR38","doi-asserted-by":"publisher","first-page":"11457","DOI":"10.1128\/JVI.79.17.11457-11466.2005","volume":"79","author":"RS Klein","year":"2005","unstructured":"Klein RS, Lin E, Zhang B, Luster AD, Tollett J, Samuel MA, Engle M, Diamond MS (2005) Neuronal CXCL10 directs CD8+ T-Cell recruitment and control of West Nile Virus encephalitis. J Virol 79:11457\u201311466. https:\/\/doi.org\/10.1128\/JVI.79.17.11457-11466.2005","journal-title":"J Virol"},{"key":"1547_CR39","unstructured":"Kolde R (2012) Pheatmap: pretty heatmaps. R package version 1"},{"key":"1547_CR40","doi-asserted-by":"publisher","first-page":"2333","DOI":"10.1126\/science.286.5448.2333","volume":"286","author":"RS Lanciotti","year":"1999","unstructured":"Lanciotti RS, Roehrig JT, Deubel V, Smith J, Parker M, Steele K, Crise B, Volpe KE, Crabtree MB, Scherret JH et al (1999) Origin of the West Nile virus responsible for an outbreak of encephalitis in the northeastern United States. Science 286:2333\u20132337. https:\/\/doi.org\/10.1126\/science.286.5448.2333","journal-title":"Science"},{"key":"1547_CR41","doi-asserted-by":"publisher","first-page":"23336","DOI":"10.1073\/pnas.1922788117","volume":"117","author":"F Lei","year":"2020","unstructured":"Lei F, Cui N, Zhou C, Chodosh J, Vavvas DG, Paschalis EI (2020) CSF1R inhibition by a small-molecule inhibitor is not microglia specific; affecting hematopoiesis and the function of macrophages. Proc Natl Acad Sci USA 117:23336\u201323338. https:\/\/doi.org\/10.1073\/pnas.1922788117","journal-title":"Proc Natl Acad Sci USA"},{"key":"1547_CR42","doi-asserted-by":"publisher","DOI":"10.1101\/2021.12.21.473532","author":"F Lei","year":"2021","unstructured":"Lei F, Cui N, Zhou C, Chodosh J, Vavvas DG, Paschalis EI (2021) CSF1R inhibition by small molecule affects T-helper cell differentiation independently of microglia depletion. bioRxiv. https:\/\/doi.org\/10.1101\/2021.12.21.473532","journal-title":"bioRxiv"},{"key":"1547_CR43","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1111\/j.1749-6632.2010.05744.x","volume":"1209","author":"G Lemke","year":"2010","unstructured":"Lemke G, Burstyn-Cohen T (2010) TAM receptors and the clearance of apoptotic cells. Ann N Y Acad Sci 1209:23\u201329. https:\/\/doi.org\/10.1111\/j.1749-6632.2010.05744.x","journal-title":"Ann N Y Acad Sci"},{"key":"1547_CR44","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.jneuroim.2014.09.014","volume":"277","author":"ND Lewis","year":"2014","unstructured":"Lewis ND, Hill JD, Juchem KW, Stefanopoulos DE, Modis LK (2014) RNA sequencing of microglia and monocyte-derived macrophages from mice with experimental autoimmune encephalomyelitis illustrates a changing phenotype with disease course. J Neuroimmunol 277:26\u201338. https:\/\/doi.org\/10.1016\/j.jneuroim.2014.09.014","journal-title":"J Neuroimmunol"},{"key":"1547_CR45","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/s0022-510x(03)00203-x","volume":"215","author":"J Li","year":"2003","unstructured":"Li J, Gran B, Zhang GX, Ventura ES, Siglienti I, Rostami A, Kamoun M (2003) Differential expression and regulation of IL-23 and IL-12 subunits and receptors in adult mouse microglia. J Neurol Sci 215:95\u2013103. https:\/\/doi.org\/10.1016\/s0022-510x(03)00203-x","journal-title":"J Neurol Sci"},{"key":"1547_CR46","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/0165-5728(89)90171-9","volume":"21","author":"Y Liu","year":"1989","unstructured":"Liu Y, King N, Kesson A, Blanden RV, Mullbacher A (1989) Flavivirus infection up-regulates the expression of class I and class II major histocompatibility antigens on and enhances T cell recognition of astrocytes in vitro. J Neuroimmunol 21:157\u2013168. https:\/\/doi.org\/10.1016\/0165-5728(89)90171-9","journal-title":"J Neuroimmunol"},{"key":"1547_CR47","doi-asserted-by":"publisher","first-page":"4980","DOI":"10.1172\/JCI99902","volume":"128","author":"H Luo","year":"2018","unstructured":"Luo H, Winkelmann ER, Zhu S, Ru W, Mays E, Silvas JA, Vollmer LL, Gao J, Peng BH, Bopp NE et al (2018) Peli1 facilitates virus replication and promotes neuroinflammation during West Nile virus infection. J Clin Investig 128:4980\u20134991. https:\/\/doi.org\/10.1172\/JCI99902","journal-title":"J Clin Investig"},{"key":"1547_CR48","doi-asserted-by":"publisher","first-page":"145","DOI":"10.3121\/cmr.1.2.145","volume":"1","author":"K Madden","year":"2003","unstructured":"Madden K (2003) West Nile virus infection and its neurological manifestations. Clin Med Res 1:145\u2013150. https:\/\/doi.org\/10.3121\/cmr.1.2.145","journal-title":"Clin Med Res"},{"key":"1547_CR49","doi-asserted-by":"publisher","first-page":"2345","DOI":"10.1002\/glia.23844","volume":"68","author":"V Mangale","year":"2020","unstructured":"Mangale V, Syage AR, Ekiz HA, Skinner DD, Cheng Y, Stone CL, Brown RM, O\u2019Connell RM, Green KN, Lane TE (2020) Microglia influence host defense, disease, and repair following murine coronavirus infection of the central nervous system. Glia 68:2345\u20132360. https:\/\/doi.org\/10.1002\/glia.23844","journal-title":"Glia"},{"key":"1547_CR50","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1080\/13550280802093927","volume":"14","author":"CP Marques","year":"2008","unstructured":"Marques CP, Cheeran MC, Palmquist JM, Hu S, Lokensgard JR (2008) Microglia are the major cellular source of inducible nitric oxide synthase during experimental herpes encephalitis. J Neurovirol 14:229\u2013238. https:\/\/doi.org\/10.1080\/13550280802093927","journal-title":"J Neurovirol"},{"key":"1547_CR51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.virusres.2006.03.009","volume":"121","author":"CP Marques","year":"2006","unstructured":"Marques CP, Hu S, Sheng W, Lokensgard JR (2006) Microglial cells initiate vigorous yet non-protective immune responses during HSV-1 brain infection. Virus Res 121:1\u201310. https:\/\/doi.org\/10.1016\/j.virusres.2006.03.009","journal-title":"Virus Res"},{"key":"1547_CR52","doi-asserted-by":"publisher","first-page":"264","DOI":"10.3389\/fncel.2014.00264","volume":"8","author":"D Michlmayr","year":"2014","unstructured":"Michlmayr D, Lim JK (2014) Chemokine receptors as important regulators of pathogenesis during arboviral encephalitis. Front Cell Neurosci 8:264. https:\/\/doi.org\/10.3389\/fncel.2014.00264","journal-title":"Front Cell Neurosci"},{"key":"1547_CR53","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abb1817","author":"EA Moseman","year":"2020","unstructured":"Moseman EA, Blanchard AC, Nayak D, McGavern DB (2020) T cell engagement of cross-presenting microglia protects the brain from a nasal virus infection. Sci Immunol. https:\/\/doi.org\/10.1126\/sciimmunol.abb1817","journal-title":"Sci Immunol"},{"key":"1547_CR54","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0102953","author":"KO Murray","year":"2014","unstructured":"Murray KO, Garcia MN, Rahbar MH, Martinez D, Khuwaja SA, Arafat RR, Rossmann S (2014) Survival analysis, long-term outcomes, and percentage of recovery up to 8 years post-infection among the Houston West Nile Virus cohort (research article). PLoS ONE. https:\/\/doi.org\/10.1371\/journal.pone.0102953","journal-title":"PLoS ONE"},{"key":"1547_CR55","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.784486","author":"D Ni","year":"2022","unstructured":"Ni D, Tan J, Niewold P, Spiteri AG, Pinget GV, Stanley D, King NJC, Macia L (2022) Impact of dietary fiber on West Nile Virus infection. Front Immunol. https:\/\/doi.org\/10.3389\/fimmu.2022.784486","journal-title":"Front Immunol"},{"key":"1547_CR56","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1111\/j.1750-3639.2003.tb00477.x","volume":"13","author":"BI Omalu","year":"2003","unstructured":"Omalu BI, Shakir AA, Wang G, Lipkin WI, Wiley CA (2003) Fatal fulminant pan-meningo-polioencephalitis due to West Nile virus. Brain Pathol 13:465\u2013472. https:\/\/doi.org\/10.1111\/j.1750-3639.2003.tb00477.x","journal-title":"Brain Pathol"},{"key":"1547_CR57","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1093\/bioinformatics\/btaa751","volume":"37","author":"D Osorio","year":"2021","unstructured":"Osorio D, Cai JJ (2021) Systematic determination of the mitochondrial proportion in human and mice tissues for single-cell RNA-sequencing data quality control. Bioinformatics 37:963\u2013967. https:\/\/doi.org\/10.1093\/bioinformatics\/btaa751","journal-title":"Bioinformatics"},{"key":"1547_CR58","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1038\/nmeth.4402","volume":"14","author":"X Qiu","year":"2017","unstructured":"Qiu X, Mao Q, Tang Y, Wang L, Chawla R, Pliner HA, Trapnell C (2017) Reversed graph embedding resolves complex single-cell trajectories. Nat Methods 14:979\u2013982. https:\/\/doi.org\/10.1038\/nmeth.4402","journal-title":"Nat Methods"},{"key":"1547_CR59","doi-asserted-by":"publisher","first-page":"13005","DOI":"10.1128\/Jvi.01994-14","volume":"88","author":"ED Quick","year":"2014","unstructured":"Quick ED, Leser JS, Clarke P, Tyler KL (2014) Activation of intrinsic immune responses and microglial phagocytosis in an ex vivo spinal cord slice culture model of West Nile Virus infection. J Virol 88:13005\u201313014. https:\/\/doi.org\/10.1128\/Jvi.01994-14","journal-title":"J Virol"},{"key":"1547_CR60","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00569-17","author":"ED Quick","year":"2017","unstructured":"Quick ED, Seitz S, Clarke P, Tyler KL (2017) Minocycline has anti-inflammatory effects and reduces cytotoxicity in an ex vivo spinal cord slice culture model of West Nile Virus infection. J Virol. https:\/\/doi.org\/10.1128\/JVI.00569-17","journal-title":"J Virol"},{"key":"1547_CR61","doi-asserted-by":"publisher","first-page":"13348","DOI":"10.1038\/ncomms13348","volume":"7","author":"LS Reinert","year":"2016","unstructured":"Reinert LS, Lopusna K, Winther H, Sun C, Thomsen MK, Nandakumar R, Mogensen TH, Meyer M, Vaegter C, Nyengaard JR et al (2016) Sensing of HSV-1 by the cGAS-STING pathway in microglia orchestrates antiviral defence in the CNS. Nat Commun 7:13348. https:\/\/doi.org\/10.1038\/ncomms13348","journal-title":"Nat Commun"},{"key":"1547_CR62","doi-asserted-by":"publisher","first-page":"e0009190","DOI":"10.1371\/journal.pntd.0009190","volume":"15","author":"SE Ronca","year":"2021","unstructured":"Ronca SE, Ruff JC, Murray KO (2021) A 20-year historical review of West Nile virus since its initial emergence in North America: Has West Nile virus become a neglected tropical disease? PLOS Negl Trop Dis 15:e0009190. https:\/\/doi.org\/10.1371\/journal.pntd.0009190","journal-title":"PLOS Negl Trop Dis"},{"key":"1547_CR63","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/s13073-022-01111-0","volume":"14","author":"SF Rosen","year":"2022","unstructured":"Rosen SF, Soung AL, Yang W, Ai S, Kanmogne M, Dave VA, Artyomov M, Magee JA, Klein RS (2022) Single-cell RNA transcriptome analysis of CNS immune cells reveals CXCL16\/CXCR6 as maintenance factors for tissue-resident T cells that drive synapse elimination. Genome Med 14:108. https:\/\/doi.org\/10.1186\/s13073-022-01111-0","journal-title":"Genome Med"},{"key":"1547_CR64","doi-asserted-by":"publisher","first-page":"e0158364","DOI":"10.1371\/journal.pone.0158364","volume":"11","author":"Z Samaan","year":"2016","unstructured":"Samaan Z, McDermid Vaz S, Bawor M, Potter TH, Eskandarian S, Loeb M (2016) Neuropsychological impact of West Nile Virus infection: an extensive neuropsychiatric assessment of 49 cases in Canada. PLoS ONE 11:e0158364. https:\/\/doi.org\/10.1371\/journal.pone.0158364","journal-title":"PLoS ONE"},{"key":"1547_CR65","doi-asserted-by":"publisher","first-page":"13350","DOI":"10.1128\/jvi.79.21.13350-13361.2005","volume":"79","author":"MA Samuel","year":"2005","unstructured":"Samuel MA, Diamond MS (2005) Alpha\/beta interferon protects against lethal West Nile virus infection by restricting cellular tropism and enhancing neuronal survival. J Virol 79:13350\u201313361. https:\/\/doi.org\/10.1128\/jvi.79.21.13350-13361.2005","journal-title":"J Virol"},{"key":"1547_CR66","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/s13365-019-00740-3","volume":"25","author":"J Sanchez","year":"2019","unstructured":"Sanchez J, DePaula-Silva A, Doty D, Truong A, Libbey J, Fujinami R (2019) Microglial cell depletion is fatal with low level picornavirus infection of the central nervous system. J Neurovirol 25:415\u2013421. https:\/\/doi.org\/10.1007\/s13365-019-00740-3","journal-title":"J Neurovirol"},{"key":"1547_CR67","doi-asserted-by":"publisher","first-page":"621090","DOI":"10.3389\/fimmu.2021.621090","volume":"12","author":"JMS Sanchez","year":"2021","unstructured":"Sanchez JMS, DePaula-Silva AB, Doty DJ, Hanak TJ, Truong A, Libbey JE, Fujinami RS (2021) The CSF1R-microglia axis has protective host-specific roles during neurotropic picornavirus infection. Front Immunol 12:621090. https:\/\/doi.org\/10.3389\/fimmu.2021.621090","journal-title":"Front Immunol"},{"key":"1547_CR68","doi-asserted-by":"publisher","first-page":"24464","DOI":"10.1073\/pnas.2007814117","volume":"117","author":"A Sariol","year":"2020","unstructured":"Sariol A, Mackin S, Allred MG, Ma C, Zhou Y, Zhang Q, Zou X, Abrahante JE, Meyerholz DK, Perlman S (2020) Microglia depletion exacerbates demyelination and impairs remyelination in a neurotropic coronavirus infection. Proc Natl Acad Sci USA 117:24464\u201324474. https:\/\/doi.org\/10.1073\/pnas.2007814117","journal-title":"Proc Natl Acad Sci USA"},{"key":"1547_CR69","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/nbt.3192","volume":"33","author":"R Satija","year":"2015","unstructured":"Satija R, Farrell JA, Gennert D, Schier AF, Regev A (2015) Spatial reconstruction of single-cell gene expression data. Nat Biotechnol 33:495\u2013502. https:\/\/doi.org\/10.1038\/nbt.3192","journal-title":"Nat Biotechnol"},{"key":"1547_CR70","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00525-18","author":"S Seitz","year":"2018","unstructured":"Seitz S, Clarke P, Tyler KL (2018) Pharmacologic depletion of microglia increases viral load in the brain and enhances mortality in murine models of flavivirus-induced encephalitis. J Virol. https:\/\/doi.org\/10.1128\/JVI.00525-18","journal-title":"J Virol"},{"key":"1547_CR71","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-022-01275-6","author":"QH Shan","year":"2022","unstructured":"Shan QH, Qin XY, Zhou N, Huang C, Wang Y, Chen P, Zhou JN (2022) A method for ultrafast tissue clearing that preserves fluorescence for multimodal and longitudinal brain imaging. BMC Biol. https:\/\/doi.org\/10.1186\/s12915-022-01275-6","journal-title":"BMC Biol"},{"key":"1547_CR72","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/j.immuni.2013.02.012","volume":"38","author":"R Shechter","year":"2013","unstructured":"Shechter R, Miller O, Yovel G, Rosenzweig N, London A, Ruckh J, Kim K-W, Klein E, Kalchenko V, Bendel P (2013) Recruitment of beneficial M2 macrophages to injured spinal cord is orchestrated by remote brain choroid plexus. Immunity 38:555\u2013569","journal-title":"Immunity"},{"key":"1547_CR73","doi-asserted-by":"publisher","first-page":"3758","DOI":"10.1038\/s41467-019-11674-z","volume":"10","author":"E Spangenberg","year":"2019","unstructured":"Spangenberg E, Severson PL, Hohsfield LA, Crapser J, Zhang J, Burton EA, Zhang Y, Spevak W, Lin J, Phan NY et al (2019) Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer\u2019s disease model. Nat Commun 10:3758. https:\/\/doi.org\/10.1038\/s41467-019-11674-z","journal-title":"Nat Commun"},{"key":"1547_CR74","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.4103\/1673-5374.360170","volume":"18","author":"AG Spiteri","year":"2023","unstructured":"Spiteri AG, King NJC (2023) Putting PLX5622 into perspective: microglia in central nervous system viral infection. Neural Regen Res 18:1269\u20131270. https:\/\/doi.org\/10.4103\/1673-5374.360170","journal-title":"Neural Regen Res"},{"key":"1547_CR75","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.851556","author":"AG Spiteri","year":"2022","unstructured":"Spiteri AG, Ni D, Ling ZL, Macia L, Campbell IL, Hofer MJ, King NJC (2022) PLX5622 reduces disease severity in lethal CNS infection by off-target inhibition of peripheral inflammatory monocyte production. Front Immunol. https:\/\/doi.org\/10.3389\/fimmu.2022.851556","journal-title":"Front Immunol"},{"key":"1547_CR76","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1186\/s12974-021-02214-y","volume":"18","author":"AG Spiteri","year":"2021","unstructured":"Spiteri AG, Terry RL, Wishart CL, Ashhurst TM, Campbell IL, Hofer MJ, King NJC (2021) High-parameter cytometry unmasks microglial cell spatio-temporal response kinetics in severe neuroinflammatory disease. J Neuroinflamm 18:166. https:\/\/doi.org\/10.1186\/s12974-021-02214-y","journal-title":"J Neuroinflamm"},{"key":"1547_CR77","doi-asserted-by":"publisher","first-page":"600822","DOI":"10.3389\/fimmu.2020.600822","volume":"11","author":"AG Spiteri","year":"2020","unstructured":"Spiteri AG, Wishart CL, King NJC (2020) Immovable object meets unstoppable force? Dialogue between resident and peripheral myeloid cells in the inflamed brain. Front Immunol 11:600822. https:\/\/doi.org\/10.3389\/fimmu.2020.600822","journal-title":"Front Immunol"},{"key":"1547_CR78","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/s00401-021-02384-2","volume":"143","author":"AG Spiteri","year":"2022","unstructured":"Spiteri AG, Wishart CL, Pamphlett R, Locatelli G, King NJC (2022) Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function. Acta Neuropathol 143:179\u2013224. https:\/\/doi.org\/10.1007\/s00401-021-02384-2","journal-title":"Acta Neuropathol"},{"key":"1547_CR79","doi-asserted-by":"publisher","first-page":"e0068522","DOI":"10.1128\/spectrum.00685-22","volume":"10","author":"S Stonedahl","year":"2022","unstructured":"Stonedahl S, Leser JS, Clarke P, Tyler KL (2022) Depletion of microglia in an ex vivo brain slice culture model of West Nile Virus infection leads to increased viral titers and cell death. Microbiol Spectr 10:e0068522. https:\/\/doi.org\/10.1128\/spectrum.00685-22","journal-title":"Microbiol Spectr"},{"key":"1547_CR80","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1186\/s12864-018-4772-0","volume":"19","author":"K Street","year":"2018","unstructured":"Street K, Risso D, Fletcher RB, Das D, Ngai J, Yosef N, Purdom E, Dudoit S (2018) Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics. BMC Genomics 19:477. https:\/\/doi.org\/10.1186\/s12864-018-4772-0","journal-title":"BMC Genomics"},{"key":"1547_CR81","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","volume":"177","author":"T Stuart","year":"2019","unstructured":"Stuart T, Butler A, Hoffman P, Hafemeister C, Papalexi E, Mauck WM 3rd, Hao Y, Stoeckius M, Smibert P, Satija R (2019) Comprehensive integration of single-cell data. Cell 177:1888-1902.e1821. https:\/\/doi.org\/10.1016\/j.cell.2019.05.031","journal-title":"Cell"},{"key":"1547_CR82","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01295-20","author":"AR Syage","year":"2020","unstructured":"Syage AR, Ekiz HA, Skinner DD, Stone C, O\u2019Connell RM, Lane TE (2020) Single-cell RNA sequencing reveals the diversity of the immunological landscape following central nervous system infection by a Murine coronavirus. J Virol. https:\/\/doi.org\/10.1128\/JVI.01295-20","journal-title":"J Virol"},{"key":"1547_CR83","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1159\/000365972","volume":"7","author":"RL Terry","year":"2015","unstructured":"Terry RL, Deffrasnes C, Getts DR, Minten C, Van Vreden C, Ashhurst TM, Getts MT, Xie RDV, Campbell IL, King NJ (2015) Defective inflammatory monocyte development in IRF8-deficient mice abrogates migration to the West Nile virus-infected brain. J Innate Immun 7:102\u2013112","journal-title":"J Innate Immun"},{"key":"1547_CR84","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1186\/1742-2094-9-270","volume":"9","author":"RL Terry","year":"2012","unstructured":"Terry RL, Getts DR, Deffrasnes C, van Vreden C, Campbell IL, King NJ (2012) Inflammatory monocytes and the pathogenesis of viral encephalitis. J Neuroinflamm 9:270. https:\/\/doi.org\/10.1186\/1742-2094-9-270","journal-title":"J Neuroinflamm"},{"key":"1547_CR85","doi-asserted-by":"publisher","first-page":"3804","DOI":"10.4049\/jimmunol.176.6.3804","volume":"176","author":"T Town","year":"2006","unstructured":"Town T, Jeng D, Alexopoulou L, Tan J, Flavell RA (2006) Microglia recognize double-stranded RNA via TLR3. J Immunol 176:3804\u20133812","journal-title":"J Immunol"},{"key":"1547_CR86","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/nbt.2859","volume":"32","author":"C Trapnell","year":"2014","unstructured":"Trapnell C, Cacchiarelli D, Grimsby J, Pokharel P, Li S, Morse M, Lennon NJ, Livak KJ, Mikkelsen TS, Rinn JL (2014) The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells. Nat Biotechnol 32:381\u2013386. https:\/\/doi.org\/10.1038\/nbt.2859","journal-title":"Nat Biotechnol"},{"key":"1547_CR87","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/nri1001","volume":"3","author":"G Trinchieri","year":"2003","unstructured":"Trinchieri G (2003) Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 3:133\u2013146. https:\/\/doi.org\/10.1038\/nri1001","journal-title":"Nat Rev Immunol"},{"key":"1547_CR88","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222212457","author":"MS Tsai","year":"2021","unstructured":"Tsai MS, Wang LC, Tsai HY, Lin YJ, Wu HL, Tzeng SF, Hsu SM, Chen SH (2021) Microglia reduce herpes simplex virus 1 lethality of mice with decreased T cell and interferon responses in brains. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms222212457","journal-title":"Int J Mol Sci"},{"key":"1547_CR89","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1097\/00001756-199806220-00029","volume":"9","author":"Y Tsuyuki","year":"1998","unstructured":"Tsuyuki Y, Fujimaki H, Hikawa N, Fujita K, Nagata T, Minami M (1998) IFN-gamma induces coordinate expression of MHC class I-mediated antigen presentation machinery molecules in adult mouse Schwann cells. NeuroReport 9:2071\u20132075. https:\/\/doi.org\/10.1097\/00001756-199806220-00029","journal-title":"NeuroReport"},{"key":"1547_CR90","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1056\/NEJMra1708714","volume":"379","author":"KL Tyler","year":"2018","unstructured":"Tyler KL (2018) Acute viral encephalitis. N Engl J Med 379:557\u2013566. https:\/\/doi.org\/10.1056\/NEJMra1708714","journal-title":"N Engl J Med"},{"key":"1547_CR91","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2019.1621149","author":"S Ulbert","year":"2019","unstructured":"Ulbert S (2019) West Nile virus vaccines\u2014current situation and future directions. Hum Vaccine Immunother. https:\/\/doi.org\/10.1080\/21645515.2019.1621149","journal-title":"Hum Vaccine Immunother"},{"key":"1547_CR92","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01428-20","author":"O Uyar","year":"2020","unstructured":"Uyar O, Laflamme N, Piret J, Venable MC, Carbonneau J, Zarrouk K, Rivest S, Boivin G (2020) An early microglial response is needed to efficiently control herpes simplex virus encephalitis. J Virol. https:\/\/doi.org\/10.1128\/JVI.01428-20","journal-title":"J Virol"},{"key":"1547_CR93","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0022-1759(89)90178-6","volume":"124","author":"N Van Rooijen","year":"1989","unstructured":"Van Rooijen N (1989) The liposome-mediated macrophage \u201csuicide\u201d technique. J Immunol Methods 124:1\u20136. https:\/\/doi.org\/10.1016\/0022-1759(89)90178-6","journal-title":"J Immunol Methods"},{"key":"1547_CR94","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/0022-1759(94)90012-4","volume":"174","author":"N Van Rooijen","year":"1994","unstructured":"Van Rooijen N, Sanders A (1994) Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications. J Immunol Methods 174:83\u201393. https:\/\/doi.org\/10.1016\/0022-1759(94)90012-4","journal-title":"J Immunol Methods"},{"key":"1547_CR95","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1007\/BF00217308","volume":"238","author":"N van Rooijen","year":"1984","unstructured":"van Rooijen N, van Nieuwmegen R (1984) Elimination of phagocytic cells in the spleen after intravenous injection of liposome-encapsulated dichloromethylene diphosphonate. An enzyme-histochemical study. Cell Tissue Res 238:355\u2013358. https:\/\/doi.org\/10.1007\/BF00217308","journal-title":"Cell Tissue Res"},{"key":"1547_CR96","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1002\/glia.24164","volume":"70","author":"E Vankriekelsvenne","year":"2022","unstructured":"Vankriekelsvenne E, Chrzanowski U, Manzhula K, Greiner T, Wree A, Hawlitschka A, Llovera G, Zhan J, Joost S, Schmitz C et al (2022) Transmembrane protein 119 is neither a specific nor a reliable marker for microglia. Glia 70:1170\u20131190. https:\/\/doi.org\/10.1002\/glia.24164","journal-title":"Glia"},{"key":"1547_CR97","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1038\/nature18283","volume":"534","author":"MJ Vasek","year":"2016","unstructured":"Vasek MJ, Garber C, Dorsey D, Durrant DM, Bollman B, Soung A, Yu J, Perez-Torres C, Frouin A, Wilton DK et al (2016) A complement-microglial axis drives synapse loss during virus-induced memory impairment. Nature 534:538\u2013543. https:\/\/doi.org\/10.1038\/nature18283","journal-title":"Nature"},{"key":"1547_CR98","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1212\/WNL.0000000000000086","volume":"82","author":"NM Vora","year":"2014","unstructured":"Vora NM, Holman RC, Mehal JM, Steiner CA, Blanton J, Sejvar J (2014) Burden of encephalitis-associated hospitalizations in the United States, 1998\u20132010. Neurology 82:443\u2013451. https:\/\/doi.org\/10.1212\/WNL.0000000000000086","journal-title":"Neurology"},{"key":"1547_CR99","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2018.09.006","author":"I Waltl","year":"2018","unstructured":"Waltl I, K\u00e4ufer C, Gerhauser I, Chhatbar C, Ghita L, Kalinke U, L\u00f6scher W (2018) Microglia have a protective role in viral encephalitis-induced seizure development and hippocampal damage. Brain Behav Immun. https:\/\/doi.org\/10.1016\/j.bbi.2018.09.006","journal-title":"Brain Behav Immun"},{"key":"1547_CR100","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.1038\/nm1140","volume":"10","author":"T Wang","year":"2004","unstructured":"Wang T, Fikrig E, Town T, Flavell RA, Alexopoulou L, Anderson JF (2004) Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nat Med 10:1366\u20131373. https:\/\/doi.org\/10.1038\/nm1140","journal-title":"Nat Med"},{"key":"1547_CR101","doi-asserted-by":"publisher","first-page":"13323","DOI":"10.1128\/jvi.77.24.13323-13334.2003","volume":"77","author":"Y Wang","year":"2003","unstructured":"Wang Y, Lobigs M, Lee E, Mullbacher A (2003) CD8+ T cells mediate recovery and immunopathology in West Nile virus encephalitis. J Virol 77:13323\u201313334. https:\/\/doi.org\/10.1128\/jvi.77.24.13323-13334.2003","journal-title":"J Virol"},{"key":"1547_CR102","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.4269\/ajtmh.14-0616","volume":"92","author":"JE Weatherhead","year":"2015","unstructured":"Weatherhead JE, Miller VE, Garcia MN, Hasbun R, Salazar L, Dimachkie MM, Murray KO (2015) Long-term neurological outcomes in West Nile virus-infected patients: an observational study. Am J Trop Med Hyg 92:1006\u20131012. https:\/\/doi.org\/10.4269\/ajtmh.14-0616","journal-title":"Am J Trop Med Hyg"},{"key":"1547_CR103","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1172\/JCI97229","volume":"128","author":"DL Wheeler","year":"2018","unstructured":"Wheeler DL, Sariol A, Meyerholz DK, Perlman S (2018) Microglia are required for protection against lethal coronavirus encephalitis in mice. J Clin Invest 128:931\u2013943. https:\/\/doi.org\/10.1172\/JCI97229","journal-title":"J Clin Invest"},{"key":"1547_CR104","unstructured":"Wickham H (2006) An introduction to ggplot: An implementation of the grammar of graphics in R. Statistics"},{"key":"1547_CR105","unstructured":"Wickham H, Wickham MH (2007) The ggplot package. Google Scholar, City"},{"key":"1547_CR106","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.7404.1","author":"ER Winkelmann","year":"2016","unstructured":"Winkelmann ER, Luo H, Wang T (2016) West Nile Virus infection in the central nervous system. F1000Research. https:\/\/doi.org\/10.12688\/f1000research.7404.1","journal-title":"F1000Research"},{"key":"1547_CR107","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24314","author":"CL Wishart","year":"2022","unstructured":"Wishart CL, Spiteri AG, Locatelli G, King NJC (2022) Integrating transcriptomic datasets across neurological disease identifies unique myeloid subpopulations driving disease-specific signatures. Glia. https:\/\/doi.org\/10.1002\/glia.24314","journal-title":"Glia"},{"key":"1547_CR108","doi-asserted-by":"publisher","first-page":"2641","DOI":"10.4049\/jimmunol.180.4.2641","volume":"180","author":"B Zhang","year":"2008","unstructured":"Zhang B, Chan YK, Lu B, Diamond MS, Klein RS (2008) CXCR3 Mediates region-specific antiviral T cell trafficking within the central nervous system during West Nile Virus encephalitis. J Immunol 180:2641","journal-title":"J Immunol"},{"key":"1547_CR109","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1080\/08830180902978120","volume":"28","author":"F Zhou","year":"2009","unstructured":"Zhou F (2009) Molecular mechanisms of IFN-gamma to up-regulate MHC class I antigen processing and presentation. Int Rev Immunol 28:239\u2013260. https:\/\/doi.org\/10.1080\/08830180902978120","journal-title":"Int Rev Immunol"},{"key":"1547_CR110","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1007\/s13365-016-0508-6","volume":"23","author":"J Zimmermann","year":"2017","unstructured":"Zimmermann J, Hafezi W, Dockhorn A, Lorentzen EU, Krauthausen M, Getts DR, Muller M, Kuhn JE, King NJC (2017) Enhanced viral clearance and reduced leukocyte infiltration in experimental herpes encephalitis after intranasal infection of CXCR3-deficient mice. J Neurovirol 23:394\u2013403. https:\/\/doi.org\/10.1007\/s13365-016-0508-6","journal-title":"J Neurovirol"}],"container-title":["Acta Neuropathologica Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-023-01547-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40478-023-01547-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-023-01547-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T00:40:18Z","timestamp":1680741618000},"score":1,"resource":{"primary":{"URL":"https:\/\/actaneurocomms.biomedcentral.com\/articles\/10.1186\/s40478-023-01547-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,4]]},"references-count":110,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["1547"],"URL":"https:\/\/doi.org\/10.1186\/s40478-023-01547-4","relation":{},"ISSN":["2051-5960"],"issn-type":[{"value":"2051-5960","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,4]]},"assertion":[{"value":"27 January 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 March 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 April 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential competing interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"60"}}