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J Allergy Clin Immunol. 2011 Feb;127(2):430-438.e1-2. doi: 10.1016/j.jaci.2010.11.013. Epub 2011 Jan 5.

Specificity protein 1 is pivotal in the skin's antiviral response.

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  • 1Department of Pediatrics, National Jewish Health, Denver, Colo, USA.

Abstract

BACKGROUND:

Previous studies have found specificity protein (Sp) 1 transcription factor in the viral replication machinery and postulated that Sp1 was required for viral replication in host cells.

OBJECTIVES:

We investigated the role of Sp1 in the skin's antiviral responses from the perspective of host defense and its biological relevance in patients with atopic dermatitis and a history of eczema herpeticum (ADEH(+)).

METHODS:

Small interfering RNA duplexes were used to knock down Sp1 in keratinocytes. The expression of vaccinia virus (VV), herpes simplex virus 1, and other genes were evaluated by real-time PCR, or combined with Western blot and immunohistofluorescence staining. A total of 106 human subjects participated in this study.

RESULTS:

Both VV and herpes simplex virus 1 replication were enhanced in Sp1 knocked-down keratinocytes. Sp1 gene expression was significantly decreased in ADEH(+) subjects compared with patients with atopic dermatitis without a history of eczema herpeticum and nonatopic subjects (P < .0001) and inversely correlated with VV DNA copy number in human skin explants incubated with VV in vitro (partial correlation r = -0.256; P = .009). Gene profiling revealed that the antiviral genes, double-stranded RNA-dependent protein kinase (PKR) and 2'5'-oligoadenylate synthetase 2 (OAS2), were significantly downregulated in Sp1-silenced keratinocytes. Gene expression of PKR and OAS2 was also significantly decreased in skin biopsies from ADEH(+) subjects compared with patients with atopic dermatitis without a history of eczema herpeticum and nonatopic subjects. IFN-γ augmented the antiviral capacity of Sp1-silenced keratinocytes.

CONCLUSION:

Specificity protein 1 knockdown enhances viral replication in keratinocytes by downregulating gene expression of PKR and OAS2. Sp1 deficiency in ADEH(+) patients may contribute to their increased propensity to disseminated skin viral infections. IFN-γ augmentation may be a potential treatment for ADEH(+) patients.

Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

PMID:
21208652
[PubMed - indexed for MEDLINE]
PMCID:
PMC3734863
Free PMC Article

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