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TBEV pathogenesis may occur directly via virus-induced damage to neurons or through immunopathology due to excessive inflammation. While primary cells isolated from the host can be used to study the immune response to TBEV, it is still unclear how well these reflect the immune response elicited in vivo. Here, we compared the transcriptional response to TBEV and the less pathogenic tick-borne flavivirus, Langat virus (LGTV), in primary monocultures of neurons, astrocytes and microglia in vitro, with the transcriptional response in vivo captured by single-nuclei RNA sequencing (snRNA-seq) of a whole mouse cortex. We detected similar transcriptional changes induced by both LGTV and TBEV infection in vitro, with the lower response to LGTV likely resulting from slower viral kinetics. Gene set enrichment analysis showed a stronger transcriptional response in vivo than in vitro for astrocytes and microglia, with a limited overlap mainly dominated by interferon signaling. Together, this adds to our understanding of neurotropic flavivirus pathogenesis and the strengths and limitations of available model systems.<\/jats:p>","DOI":"10.3390\/v16081327","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T01:38:45Z","timestamp":1724117925000},"page":"1327","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Transcriptional Response to Tick-Borne Flavivirus Infection in Neurons, Astrocytes and Microglia In Vivo and In Vitro"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8512-0535","authenticated-orcid":false,"given":"Ebba","family":"Rosendal","sequence":"first","affiliation":[{"name":"Department of Clinical Microbiology, Ume\u00e5 University, 90185 Ume\u00e5, Sweden"},{"name":"The Laboratory for Molecular Infection Medicine Sweden (MIMS), Ume\u00e5 University, 90187 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Lindqvist","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Ume\u00e5 University, 90185 Ume\u00e5, Sweden"},{"name":"The Laboratory for Molecular Infection Medicine Sweden (MIMS), Ume\u00e5 University, 90187 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3214-6605","authenticated-orcid":false,"given":"Nunya","family":"Chotiwan","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Ume\u00e5 University, 90185 Ume\u00e5, Sweden"},{"name":"The Laboratory for Molecular Infection Medicine Sweden (MIMS), Ume\u00e5 University, 90187 Ume\u00e5, Sweden"},{"name":"Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakarn 10540, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7745-2844","authenticated-orcid":false,"given":"Johan","family":"Henriksson","sequence":"additional","affiliation":[{"name":"The Laboratory for Molecular Infection Medicine Sweden (MIMS), Ume\u00e5 University, 90187 Ume\u00e5, Sweden"},{"name":"Department of Molecular Biology, Icelab, Ume\u00e5 Centre for Microbial Research (UCMR), Ume\u00e5 University, 90187 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6553-0940","authenticated-orcid":false,"given":"Anna K.","family":"\u00d6verby","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Ume\u00e5 University, 90185 Ume\u00e5, Sweden"},{"name":"The Laboratory for Molecular Infection Medicine Sweden (MIMS), Ume\u00e5 University, 90187 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1159\/000324023","article-title":"Experimental infection of goats with tick-borne encephalitis virus and the possibilities to prevent virus transmission by raw goat milk","volume":"55","author":"Balogh","year":"2011","journal-title":"Intervirology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"806","DOI":"10.3201\/eid1905.121442","article-title":"Tick-borne encephalitis associated with consumption of raw goat milk, Slovenia, 2012","volume":"19","author":"Hudopisk","year":"2013","journal-title":"Emerg. 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