Journal
JOURNAL OF VIROLOGY
Volume 79, Issue 12, Pages 7514-7527Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.79.12.7514-7527.2005
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Funding
- NIMH NIH HHS [MH62261, MH62231, P30 MH062261, R01 MH062231] Funding Source: Medline
- NINDS NIH HHS [NS36979, R01 NS036979] Funding Source: Medline
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Interferon regulatory factors (IRFs) are a family of transcription factors involved in the regulation of the interferons (IFNs) and other genes that may have an essential role in antiviral defense in the central nervous system, although this is currently not well defined. Therefore, we examined the regulation of IRF gene expression in the brain during viral infection. Several IRF genes (IRF-2, -3, -5, -7, and -9) were expressed at low levels in the brain of uninfected mice. Following intracranial infection with lymphocytic choriomeningitis virus (LCW), expression of the IRF-7 and IRF-9 genes increased significantly by day 2. IRF-7 and IRF-9 gene expression in the brain was widespread at sites of LCMV infection, with the highest levels in infiltrating mononuclear cells, microglia/macrophages, and neurons. IRF-7 and IRF-9 gene expression was increased in LCW-infected brain from IFN-gamma knockout (KO) but not IFN-alpha/beta R KO animals. In the brain, spleen, and liver or cultured glial and spleen cells, IRF-7 but not IRF-9 gene expression increased with delayed kinetics in the absence of STAT1 but not STAT2 following LCMV infection or IFN-alpha treatment, respectively. The stimulation of IRF-7 gene expression by IFN-alpha in glial cell culture was prevented by cycloheximide. Thus, (i) many of the IRF genes were expressed constitutively in the mouse brain; (ii) the IRF-7 and IRF-9 genes were upregulated during viral infection, a process dependent on IFN-alpha/beta but not IFN-gamma; and (iii) IRF-7 but not IRF-9 gene expression can be stimulated in a STAT1-independent but STAT2-dependent fashion via unidentified indirect pathways coupled to the activation of the IFN-alpha/beta receptor.
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