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Published on: March 8, 2012
Epigallocatechin-3-gallate Can Prevent Type 2 Human Papillomavirus E7 from Suppressing Interferon-Stimulated Genes
Ji Young Song1,2, Ju Hee Han2, Yumee Song2
1Program of Immunology & Microbiology, Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Korea.
Abstract:
Human papillomavirus (HPV) in high-risk groups is known to suppress the type I interferon (IFN) signaling pathway leading to the transcription of interferon-stimulated genes (ISGs), which have many antiviral functions. However, the effects of HPV on the action of various ISGs in low-risk groups are not fully understood. We aimed to investigate whether antiviral ISGs are expressed in transfected keratinocytes with type 2 HPV (HPV-2) E7. The mRNA and protein expressions of ISGs and type I IFN signaling pathway components were evaluated by quantitative real-time polymerase chain reaction, western blot, immunofluorescence, and/or immunohistochemistry. Compared with normal skin, mRNA expression of all ISGs in HPV-2 positive cutaneous warts was significantly decreased (p < 0.05). In comparison with empty vector transfection, E7 transfection significantly down-regulated the mRNA and protein expressions of ISGs and type I IFN signaling pathway components, which were significantly up-regulated by E7 siRNA transfection (p < 0.05). Interestingly, epigallocatechin-3-gallate (EGCG) pretreatment up-regulated the mRNA and protein expressions of ISGs and type I IFN signaling pathway components, which were significantly down-regulated by E7 transfection (p < 0.05). Our results demonstrate that EGCG is a potential candidate for cutaneous wart prevention.
Insights
Low-risk human papillomavirus (HPV) type 2 E7 protein suppresses antiviral interferon-stimulated genes (ISGs). Epigallocatechin-3-gallate (EGCG) may prevent cutaneous warts by upregulating these ISGs.
Area of Science:
- Virology
- Immunology
- Dermatology
Background:
- High-risk human papillomavirus (HPV) suppresses type I interferon (IFN) signaling and interferon-stimulated genes (ISGs).
- The impact of low-risk HPV on ISG expression and antiviral functions remains unclear.
Purpose of the Study:
- To investigate the expression of antiviral ISGs in keratinocytes transfected with the type 2 HPV (HPV-2) E7 protein.
- To evaluate the potential of epigallocatechin-3-gallate (EGCG) in modulating HPV-induced ISG suppression.
Main Methods:
- Quantitative real-time polymerase chain reaction (qPCR) to assess mRNA expression.
- Western blot and immunofluorescence/immunohistochemistry to evaluate protein expression.
- Transfection with HPV-2 E7, E7 siRNA, and EGCG pretreatment in keratinocytes.
Main Results:
- HPV-2 positive cutaneous warts showed significantly decreased ISG mRNA expression compared to normal skin.
- HPV-2 E7 transfection significantly downregulated ISG and type I IFN signaling pathway components.
- EGCG pretreatment upregulated ISG and type I IFN signaling pathway components suppressed by HPV-2 E7.
Conclusions:
- The E7 protein of low-risk HPV-2 downregulates antiviral ISGs and type I IFN signaling.
- EGCG demonstrates potential as a preventive agent for cutaneous warts by restoring ISG expression.
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