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

Int J Mol Sci. 2021 Feb 28;22(5):2418. doi: 10.3390/ijms22052418.

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.

Keywords: E7; epigallocatechin-3-gallate; human papillomavirus; interferon-stimulated genes; type I IFN signaling pathway.

MeSH terms

  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Catechin / therapeutic use
  • Cell Line
  • Gene Expression Regulation*
  • HaCaT Cells
  • Humans
  • Interferon Type I / metabolism*
  • Papillomaviridae / metabolism*
  • Papillomavirus E7 Proteins / metabolism*
  • Papillomavirus Infections / drug therapy*
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / immunology
  • Signal Transduction

Substances

  • Antiviral Agents
  • Interferon Type I
  • Papillomavirus E7 Proteins
  • Catechin
  • epigallocatechin gallate