{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T01:35:23Z","timestamp":1782437723136,"version":"3.54.5"},"reference-count":73,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T00:00:00Z","timestamp":1626998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["398066876\/GRK 2485\/1"],"award-info":[{"award-number":["398066876\/GRK 2485\/1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["158989968\u2014SFB 900\u2010B2"],"award-info":[{"award-number":["158989968\u2014SFB 900\u2010B2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01KI1719"],"award-info":[{"award-number":["01KI1719"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009318","name":"Helmholtz Association","doi-asserted-by":"publisher","award":["ZT\u20100027"],"award-info":[{"award-number":["ZT\u20100027"]}],"id":[{"id":"10.13039\/501100009318","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Tick\u2010borne encephalitis virus (TBEV), a member of the\n                    <jats:italic>Flaviviridae<\/jats:italic>\n                    family, is typically transmitted upon tick bite and can cause meningitis and encephalitis in humans. In TBEV\u2010infected mice, mitochondrial antiviral\u2010signaling protein (MAVS), the downstream adaptor of retinoic acid\u2010inducible gene\u2010I (RIG\u2010I)\u2010like receptor (RLR) signaling, is needed to induce early type I interferon (IFN) responses and to confer protection. To characterize the brain\u2010resident cell subset that produces protective IFN\u2010\u03b2 in TBEV\u2010infected mice, we isolated neurons, astrocytes, and microglia from mice and exposed these cell types to TBEV in vitro. Under such conditions, neurons showed the highest percentage of infected cells, whereas astrocytes and microglia were infected to a lesser extent. In the supernatant (SN) of infected neurons, IFN\u2010\u03b2 was not detectable, while infected astrocytes showed high and microglia low IFN\u2010\u03b2 expression. Transcriptome analyses of astrocytes implied that MAVS signaling was needed early after TBEV infection. Accordingly, MAVS\u2010deficient astrocytes showed enhanced TBEV infection and significantly reduced early IFN\u2010\u03b2 responses. Nevertheless, at later time points, moderate amounts of IFN\u2010\u03b2 were detected in the SN of infected MAVS\u2010deficient astrocytes. Transcriptome analyses indicated that MAVS deficiency negatively affected the induction of early anti\u2010viral responses, which resulted in significantly increased TBEV replication. Treatment with MyD88 and TRIF inhibiting peptides reduced only late IFN\u2010\u03b2 responses of TBEV\u2010infected WT astrocytes and blocked entirely IFN\u2010\u03b2 responses of infected MAVS\u2010deficient astrocytes. Thus, upon TBEV exposure of brain\u2010resident cells, astrocytes are important IFN\u2010\u03b2 producers showing biphasic IFN\u2010\u03b2 induction that initially depends on MAVS and later on MyD88\/TRIF signaling.\n                  <\/jats:p>","DOI":"10.1002\/jnr.24923","type":"journal-article","created":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T07:17:57Z","timestamp":1627024677000},"page":"2478-2492","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Sequential MAVS and MyD88\/TRIF signaling triggers anti\u2010viral responses of tick\u2010borne encephalitis virus\u2010infected murine astrocytes"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6736-6355","authenticated-orcid":false,"given":"Luca","family":"Ghita","sequence":"first","affiliation":[{"name":"Institute for Experimental Infection Research TWINCORE Centre for Experimental and Clinical Infection Research a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Breitkopf","sequence":"additional","affiliation":[{"name":"Institute for Biochemistry and Research Center for Emerging Infections and Zoonoses (RIZ) University of Veterinary Medicine Hannover, Foundation Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Mulenge","sequence":"additional","affiliation":[{"name":"Institute for Experimental Infection Research TWINCORE Centre for Experimental and Clinical Infection Research a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Pavlou","sequence":"additional","affiliation":[{"name":"Institute for Experimental Infection Research TWINCORE Centre for Experimental and Clinical Infection Research a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School Hannover Germany"},{"name":"Clinical Neuroimmunology and Neurochemistry Department of Neurology Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia Luise","family":"Gern","sequence":"additional","affiliation":[{"name":"Institute for Experimental Infection Research TWINCORE Centre for Experimental and Clinical Infection Research a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School Hannover Germany"},{"name":"Department of Pathology University of Veterinary Medicine Hannover, Foundation Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ver\u00f3nica","family":"Dur\u00e1n","sequence":"additional","affiliation":[{"name":"Institute for Experimental Infection Research TWINCORE Centre for Experimental and Clinical Infection Research a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chittappen Kandiyil","family":"Prajeeth","sequence":"additional","affiliation":[{"name":"Clinical Neuroimmunology and Neurochemistry Department of Neurology Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Kohls","sequence":"additional","affiliation":[{"name":"Institute for Animal Breeding and Genetics University of Veterinary Medicine Hannover, Foundation Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Jung","sequence":"additional","affiliation":[{"name":"Institute for Animal Breeding and Genetics University of Veterinary Medicine Hannover, Foundation Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Stangel","sequence":"additional","affiliation":[{"name":"Clinical Neuroimmunology and Neurochemistry Department of Neurology Hannover Medical School Hannover Germany"},{"name":"Cluster of Excellence \u2010 Resolving Infection Susceptibility (RESIST, EXC 2155) Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imke","family":"Steffen","sequence":"additional","affiliation":[{"name":"Institute for Biochemistry and Research Center for Emerging Infections and Zoonoses (RIZ) University of Veterinary Medicine Hannover, Foundation Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0503-9564","authenticated-orcid":false,"given":"Ulrich","family":"Kalinke","sequence":"additional","affiliation":[{"name":"Institute for Experimental Infection Research TWINCORE Centre for Experimental and Clinical Infection Research a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School Hannover Germany"},{"name":"Cluster of Excellence \u2010 Resolving Infection Susceptibility (RESIST, EXC 2155) Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7,23]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80596-8"},{"key":"e_1_2_13_3_1","first-page":"1800201","article-title":"Tick\u2010borne encephalitis in Europe, 2012 to 2016","volume":"23","author":"Beaute J.","year":"2018","journal-title":"Euro Surveillance: Bulletin Europeen sur les Maladies Transmissibles = European Communicable Disease Bulletin"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bth088"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.20.12828-12839.2005"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep10745"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2013.10.012"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402064"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.05.040"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02044-14"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.11.4957-4966.2000"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1086\/515195"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01756-x"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.6.2913-2923.2006"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01305-07"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/13550280802337217"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.05.007"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-3542(02)00206-1"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2012.12.024"},{"key":"e_1_2_13_21_1","first-page":"201","article-title":"Tick\u2010borne encephalitis and the impact of vaccination","volume":"18","author":"Heinz F. X.","year":"2004","journal-title":"Archives of Virology Supplementum"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens8020042"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500079"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.06.041"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60582-9"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1863"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.05.006"},{"key":"e_1_2_13_28_1","first-page":"E050623.2","article-title":"Tickborne encephalitis outbreak in Estonia linked to raw goat milk, May\u2010June 2005","volume":"10","author":"Kerbo N.","year":"2005","journal-title":"Euro Surveillance: Bulletin Europeen sur les Maladies Transmissibles = European Communicable Disease Bulletin"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiq082"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.03.010"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.1.73-83.1998"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-016-0487-9"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ttbdis.2014.04.001"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.17.9285-9294.2004"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60800-4"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1119-3"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-016-0748-7"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.05.003"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(89)90246-8"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.011437-0"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.12036.1"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.03.013"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000926"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.068411-0"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2017.04.012"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02054-17"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.142287799"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00365-09"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02979-15"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1604"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1596-z"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0086219"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00352"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003039"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a118408"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-008-8065-6"},{"key":"e_1_2_13_58_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020472"},{"key":"e_1_2_13_59_1","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.010058-0"},{"key":"e_1_2_13_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2014.05.049"},{"key":"e_1_2_13_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1386-6532(02)00168-3"},{"key":"e_1_2_13_62_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1081315"},{"key":"e_1_2_13_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2012.06.009"},{"key":"e_1_2_13_64_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1400959"},{"key":"e_1_2_13_65_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003541"},{"key":"e_1_2_13_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2950"},{"key":"e_1_2_13_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10863-0"},{"key":"e_1_2_13_68_1","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/497987"},{"key":"e_1_2_13_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2008.01277.x"},{"key":"e_1_2_13_70_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.780122"},{"key":"e_1_2_13_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2018.07.014"},{"key":"e_1_2_13_72_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-05-430090"},{"key":"e_1_2_13_73_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1087262"},{"key":"e_1_2_13_74_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701507"}],"container-title":["Journal of Neuroscience Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.24923","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jnr.24923","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.24923","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T10:29:38Z","timestamp":1692959378000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jnr.24923"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,23]]},"references-count":73,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1002\/jnr.24923"],"URL":"https:\/\/doi.org\/10.1002\/jnr.24923","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.06.30.177485","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.1002\/JNR.24923\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.24923\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.24923\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.24923\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.24923\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.24923\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0360-4012","1097-4547"],"issn-type":[{"value":"0360-4012","type":"print"},{"value":"1097-4547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,23]]},"assertion":[{"value":"2021-03-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}