Abstract
Interferons (IFNs) direct innate and acquired immune responses and, accordingly, are used therapeutically to treat a number of diseases, yet the diverse effects they elicit are not fully understood. Here, we identified the promyelocytic leukemia zinc finger (PLZF) protein as a previously unrecognized component of the IFN response. IFN stimulated an association of PLZF with promyelocytic leukemia protein (PML) and histone deacetylase 1 (HDAC1) to induce a decisive subset of IFN-stimulated genes (ISGs). Consequently, PLZF-deficient mice had a specific ISG expression defect and as a result were more susceptible to viral infection. This susceptibility correlated with a marked decrease in the expression of the key antiviral mediators and an impaired IFN-mediated induction of natural killer cell function. These results provide new insights into the regulatory mechanisms of IFN signaling and the induction of innate antiviral immunity.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Alphavirus Infections / genetics
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Alphavirus Infections / immunology*
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Alphavirus Infections / virology
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Animals
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Cell Line, Tumor
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Fibroblasts / drug effects
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Fibroblasts / immunology
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Fibroblasts / virology
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Gene Expression Profiling
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Gene Expression Regulation
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Histone Deacetylase 1
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Histone Deacetylases / immunology
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Histone Deacetylases / metabolism
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Immunity, Innate / genetics*
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Interferon-alpha / immunology*
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Interferon-alpha / pharmacology
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Killer Cells, Natural / drug effects
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism
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Kruppel-Like Transcription Factors / genetics
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Kruppel-Like Transcription Factors / immunology
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Kruppel-Like Transcription Factors / metabolism*
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Mice
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Mice, Knockout
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Oligonucleotide Array Sequence Analysis
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Promyelocytic Leukemia Zinc Finger Protein
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Semliki forest virus / drug effects
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Semliki forest virus / immunology
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Signal Transduction / genetics
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Signal Transduction / immunology
Substances
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Interferon-alpha
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Kruppel-Like Transcription Factors
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Promyelocytic Leukemia Zinc Finger Protein
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Zbtb16 protein, mouse
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Hdac1 protein, mouse
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Histone Deacetylase 1
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Histone Deacetylases