Epigallocatechin-3-gallate Can Prevent Type 2 Human Papillomavirus E7 from Suppressing Interferon-Stimulated Genes

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.

The Association of Four Natural Molecules—EGCG, Folic Acid, Vitamin B12, and HA—To Counteract HPV Cervical Lesions: A Case Report

“…Both in vitro and in vivo pieces of evidence have already demonstrated the protective role of these natural molecules by blocking the progression of squamous intraepithelial lesions. Studies on the individual molecules demonstrated the efficacy of (i) EGCG as an antiproliferative and proapoptotic factor [ 12 , 13 , 14 , 15 , 16 , 17 ], (ii) vitamin B12 and (iii) folic acid as methylation agents that block viral proliferation and persistence [ 19 ], and (iv) HA as a physical barrier that restores the integrity of epithelium [ 22 , 23 ]. However, no studies, until this case report, have demonstrated their synergic action and especially their efficacy against the reappearance of cervical lesions.…”

“…A recent study further revealed the effect of EGCG on the interferon (IFN) pathway, which is one of the escape mechanisms of HPV. Pretreatment with EGCG of transfected keratinocytes with type 2 HPV (HPV2) E7 upregulated the IFN signaling pathway, thus reinforcing the innate antiviral immunity against HPV2 [ 16 ].…”

Combined therapy of local recombinant human interferon α1b injection and acupuncture on verruca vulgaris: a retrospective study

“…First, verruca vulgaris is infected by HPV, which infects keratinocytes and induces minimal inflammation without lysing infected cells. Moreover, HPV decreases the maturation and antigen presentation function of the antigen presenting immune cells (Langerhans cells) [ 19 ], inhibits Type I IFN signaling pathway and results in the transcription of IFN-stimulated genes with the function of anti-virus [ 20 ]. IFN induces the production of anti-viral proteins against viral protein translation and transcription, regulates immune function by TH1 and macrophage/natural killer cell, increases antigen expression of HPV on infected cells, changes the fluidity of cell membrane by decreasing viral replication and inhibits differentiation of HPV-infected cells by decreasing HPV reproduction rate [ 21 ].…”

Preventing Persistence of HPV Infection with Natural Molecules

“…When keratinocytes are transfected with type 2 HPV (HPV2) E7, the mRNA and protein expression of type I IFN signaling pathway components are significantly downregulated. EGCG pre-treatment can reverse it by significantly up-regulating them, so reinforcing innate antiviral immunity against HPV2 [ 50 ].…”