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.
abstract: Interferon (IFN) regulatory factors (IRFs) are a family of transcription factors involved in regulating type I IFN genes and other genes participating in the early antiviral host response. 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-β-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.
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jeanette Erbo
authors.initials: JE
authors.lastname: Christensen
authors.forename: Christina
authors.initials: C
authors.lastname: Fenger
authors.forename: Shohreh
authors.initials: S
authors.lastname: Issazadeh-Navikas
authors.forename: Anna
authors.initials: A
authors.lastname: Krug
authors.forename: Peter
authors.initials: P
authors.lastname: Liljestrøm
authors.forename: Stanislas
authors.initials: S
authors.lastname: Goriely
authors.forename: Søren Riis
authors.initials: SR
authors.lastname: Paludan
authors.forename: Bente
authors.initials: B
authors.lastname: Finsen
authors.forename: Jan Pravsgaard
authors.initials: JP
authors.lastname: Christensen
authors.forename: Allan Randrup
authors.initials: AR
authors.lastname: Thomsen
mesh_terms: D000818:Animals; D005260:Female; D050838:Interferon Regulatory Factor-3 / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism; D050839:Interferon Regulatory Factor-7 / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism; D007370:Interferon Type I / Q000096:biosynthesis*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009420:Nervous System / Q000276:immunology* / Q000821:virology*
chemical_list: D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; C494233:Irf3 protein, mouse; C494235:Irf7 protein, mouse