Induction of co-inhibitory molecule CTLA-4 by human papillomavirus E7 protein through downregulation of histone methyltransferase JHDM1B expression

Virology. 2019 Dec:538:111-118. doi: 10.1016/j.virol.2019.10.001. Epub 2019 Oct 2.

Abstract

Human papillomavirus causes various skin diseases and even cancer. Unfortunately, the host immune system often fails to generate effective responses against HPV infection due to the ability of HPV to evade immune-mediated eradication, although the detailed mechanisms by which HPV inhibits host antiviral immunity are not fully understood. In this study, we reported a novel role of HPV E7 oncoprotein in inducing the expression of co-inhibitory molecule cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) in cells of epithelial origin. Mechanistically, HPV E7 protein downregulated the cellular abundance of Jumonji C histone demethylase 1B (JHDM1B), increasing the levels of H3K36 methylation within the promoter region of CTLA-4. Our findings expand the current understanding of HPV-mediated immune evasion mechanisms and may be helpful in developing optimal anti-HPV therapeutic strategies and relevant drugs.

Keywords: Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4); Human papillomavirus E7; Jumonji C histone demethylase1B (JHDM1B).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • CTLA-4 Antigen / genetics
  • CTLA-4 Antigen / metabolism*
  • F-Box Proteins / genetics
  • F-Box Proteins / metabolism*
  • Histones / chemistry
  • Histones / genetics
  • Histones / metabolism
  • Host-Pathogen Interactions
  • Human papillomavirus 11 / genetics
  • Human papillomavirus 11 / metabolism*
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Methylation
  • Papillomavirus E7 Proteins / genetics
  • Papillomavirus E7 Proteins / metabolism*
  • Papillomavirus Infections / enzymology
  • Papillomavirus Infections / genetics*
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / virology
  • Promoter Regions, Genetic
  • Protein Binding

Substances

  • CTLA-4 Antigen
  • CTLA4 protein, human
  • F-Box Proteins
  • Histones
  • Papillomavirus E7 Proteins
  • Jumonji Domain-Containing Histone Demethylases
  • KDM2A protein, human