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

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.

• Authors: Lianghua Bin, Michael D Howell, Byung Eui Kim, Joanne E Streib, Clifton F Hall, Donald Y M Leung
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 127 Issue 2 Pg. 430-438.e1-2 (Feb 2011) ISSN: 1097-6825 [Electronic] United States
• PMID: 21208652 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Chemical References

• Eukaryotic Initiation Factor-2
• Sp1 Transcription Factor
• Interferon-gamma
• eIF-2 Kinase
• 2',5'-Oligoadenylate Synthetase

Topics

• 2',5'-Oligoadenylate Synthetase (physiology)
• Adult
• Cells, Cultured
• Dermatitis, Atopic (immunology, virology)
• Eukaryotic Initiation Factor-2 (physiology)
• Female
• Gene Silencing
• Humans
• Interferon-gamma (pharmacology)
• Kaposi Varicelliform Eruption (immunology, virology)
• Keratinocytes (virology)
• Male
• Middle Aged
• Skin (immunology, virology)
• Sp1 Transcription Factor (genetics, physiology)
• Vaccinia virus (physiology)
• Virus Replication
• eIF-2 Kinase (physiology)