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To better understand the mechanisms involved in virus-induced central nervous system (CNS) inflammation, we studied the influence of IRF1, -3, -7, and -9 on the transcriptional activity of key genes encoding antiviral host factors in the CNS of mice infected with lymphocytic choriomeningitis virus (LCMV). A key finding is that neither IRF3 nor IRF7 is absolutely required for induction of a type I IFN response in the LCMV-infected CNS, whereas concurrent elimination of both factors markedly reduces the virus-induced host response. This is unlike the situation in the periphery, where deficiency of IRF7 almost eliminates the LCMV-induced production of the type I IFNs. This difference is seemingly related to the local environment, as peripheral production of type I IFNs is severely reduced in intracerebrally (i.c.) infected IRF7-deficient mice, which undergo a combined infection of the CNS and peripheral organs, such as spleen and lymph nodes. Interestingly, despite the redundancy of IRF7 in initiating the type I IFN response in the CNS, the response is not abolished in IFN-\u03b2-deficient mice, as might have been expected. Collectively, these data demonstrate that the early type I IFN response to LCMV infection in the CNS is controlled by a concerted action of IRF3 and -7. Consequently this work provides strong evidence for differential regulation of the type I IFN response in the CNS versus the periphery during viral infection.<\/jats:p>","DOI":"10.1128\/jvi.07090-11","type":"journal-article","created":{"date-parts":[[2012,4,19]],"date-time":"2012-04-19T04:29:30Z","timestamp":1334809770000},"page":"7384-7392","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["Differential Impact of Interferon Regulatory Factor 7 in Initiation of the Type I Interferon Response in the Lymphocytic Choriomeningitis Virus-Infected Central Nervous System versus the Periphery"],"prefix":"10.1128","volume":"86","author":[{"given":"Jeanette Erbo","family":"Christensen","sequence":"first","affiliation":[{"name":"Department of International Health, Immunology and Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Fenger","sequence":"additional","affiliation":[{"name":"Neuroinflammation Unit, Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohreh","family":"Issazadeh-Navikas","sequence":"additional","affiliation":[{"name":"Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Krug","sequence":"additional","affiliation":[{"name":"Medical Department, Klinikum rechts der Isar, Technical University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Liljestr\u00f8m","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislas","family":"Goriely","sequence":"additional","affiliation":[{"name":"Institute for Medical Immunology, Universit\u00e9 Libre de Bruxelles, Gosselies, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren Riis","family":"Paludan","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bente","family":"Finsen","sequence":"additional","affiliation":[{"name":"Neuroinflammation Unit, Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Pravsgaard","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of International Health, Immunology and Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan Randrup","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Department of International Health, Immunology and Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.10.7832-7840.1997"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/273684a0"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20011666"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0813234106"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)11772-7"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.7.4235"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0123-04.2004"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.182.2.1079"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.1994.tb03477.x"},{"key":"e_1_3_3_11_2","first-page":"520","article-title":"Immunological unresponsiveness of nude mice to LCM virus infection","volume":"84","author":"Christoffersen PJ","year":"1976","unstructured":"ChristoffersenPJ VolkertM RygaardJ. 1976. 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