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Activation of host ...
Abstract
Ämnesord
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- Herpes simplex virus type 1 (HSV-1) induces expression of a selectin receptor, the carbohydrate epitope sialyl Lewis X (sLe(x)), at the surface of infected cells. The molecular background to this phenomenon is that a viral immediate early RNA interacts with as yet unidentified host factors, eventually resulting in transcription of three dormant host fucosyltransferase genes (FUT3, FUT5, and FUT6), whose gene products are rate-limiting for synthesis of sLe(x). The aim of the present study was to define the immediate targets for the viral RNA in this process. We found that the Protein Kinase R (PKR) inhibitors 2-aminopurine (2-AP) and C16 inhibited FUT3, FUT5, and FUT6 expression as well as HSV-1-induced expression of sLe(x), indicating a primary role of PKR as a viral RNA target. The PKR-dependent activation of the FUT genes seemed neither to involve PKR effects on translation nor to involve NF-kappaB- or JNK-dependent activation. IMD-0354, known as an inhibitor of the NF-kappaB-activating factor IKK-2, induced FUT transcription via a novel IKK-2-independent mechanism, irrespective of whether the cells were virus-infected or not. Altogether, the results suggested that PKR is the primary target for HSV-1 early RNA during induction of FUT3, FUT5, and FUT6, and that the subsequent steps in the transcriptional activation of these host genes involve a hitherto unknown IMD-0354, yet IKK-2-independent, pathway.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- dsRNA
- ICP0
- IMD-0354
- PKR
- Selectin
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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