دورية
Interferon-α Inhibits the Murine Cytomegalovirus Immediate-Early Gene Expression by Down-Regulating NF-κB Activity
| العنوان: | Interferon-α Inhibits the Murine Cytomegalovirus Immediate-Early Gene Expression by Down-Regulating NF-κB Activity |
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| المؤلفون: | Gribaudo, Giorgio, Ravaglia, Stefania, Gaboli, Mirella, Gariglio, Marisa, Cavallo, Rossana, Landolfo, Santo |
| المصدر: | Virology; August 1, 1995, Vol. 211 Issue: 1 p251-260, 10p |
| مستخلص: | Transcription of murine cytomegalovirus (MCMV) immediate-early (IE) genes is regulated by the interaction of cellular transcription factors with a strong vital enhancer controlling promoters flanking both sides of the regulatory sequence. We have previously demonstrated that interferon-α (IFN-α) inhibits MCMV replication by impairing the transcription of IE genes. To define the cis-acting elements and trans-acting factors involved in this inhibition, permissive murine fibroblasts were transfected with DNA constructs containing the chloramphenicol acetyl transferase reporter gene and portions of the IE enhancer. The region spanning -1185 to -269 relative to the IE1-3 promoter was sufficient to allow IFN-α-induced inhibition. Since this segment contains several NF-κB sites, cells were transfected with a construct containing three copies of NF-κB element in front of the homologous minimal IE1-3 promoter. Upon IFN-α treatment the reporter gene activity was strongly reduced, indicating that NF-κB binding site is sufficient to confer inhibition. The specificity of this inhibition was demonstrated by the lack of a significant effect on the activity of DNA constructs containing either a mutated NF-κB trimer or an ATF/CRE trimer. Gel shift assays with NF-κB probes revealed that MCMV infection activated NF-κB proteins, whereas IFN-α treatment significantly reduced their ability to bind NF-κB sites. In cotransfection experiments using various NF-κB subunit expression vectors and a reporter driven by three copies of an NF-κB element, activation of NF-κB-dependent transcription was observed with expression of p65 or combinations of p50-p65. Taken as a whole, these results suggest that IFN-α inhibits MCMV IE gene enhancer activity by mechanisms that decrease the availability of virus-induced NF-κB transcriptionally active in the nuclei of infected cells. Copyright 1995, 1999 Academic Press |
| قاعدة البيانات: | Supplemental Index |
Full Text Finder | تدمد: | 00426822 10960341 |
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| DOI: | 10.1006/viro.1995.1398 |