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Updated: May 10, 2026

Use of Interferon-γ Enzyme-linked Immunospot Assay to Characterize Novel T-cell Epitopes of Human Papillomavirus
13:41

Use of Interferon-γ Enzyme-linked Immunospot Assay to Characterize Novel T-cell Epitopes of Human Papillomavirus

Published on: March 8, 2012

The human papillomavirus type 16 E7 oncoprotein induces a transcriptional repressor complex on the Toll-like receptor

Uzma A Hasan1, Claudia Zannetti, Peggy Parroche

  • 1Infections and Cancer Biology Group, International Agency for Research on Cancer, Lyon 69008, France. uzma.hasan@inserm.fr

The Journal of Experimental Medicine
|June 12, 2013
PubMed

Insights

Human papillomavirus type 16 (HPV16) suppresses immunity by targeting the TLR9 sensor. The E7 oncoprotein orchestrates an epigenetic and transcriptional complex to down-regulate TLR9, impacting the interferon response to viral infections.

Area of Science:

  • Immunology
  • Virology
  • Epigenetics

Background:

  • Oncogenic viruses like HPV16 can disrupt immune responses by inhibiting innate sensors such as TLR9.
  • The precise mechanisms by which HPV16 suppresses TLR9 function remain largely unknown.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying HPV16-mediated suppression of the TLR9 innate immune sensor.
  • To investigate the role of the HPV16 E7 oncoprotein in this regulatory process.

Main Methods:

  • Infection of human epithelial cells with HPV16.
  • Analysis of transcriptional complex formation involving NF-κBp50-p65, ERα, JARID1B, and HDAC1.
  • Chromatin immunoprecipitation assays to assess binding to the TLR9 promoter.
  • Histone methylation and acetylation analysis.
  • Validation in human cervical tissues.

Main Results:

  • HPV16 E7 oncoprotein induces an inhibitory complex containing NF-κBp50-p65 and ERα.
  • This complex recruits JARID1B and HDAC1, binding the TLR9 promoter.
  • Epigenetic modifications (decreased histone methylation and acetylation) lead to TLR9 down-regulation.
  • NF-κB and ERα involvement confirmed in patient-derived cervical tissues.
  • HPV16-induced TLR9 suppression impairs the interferon response.

Conclusions:

  • A novel mechanism of HPV16-mediated immune evasion involves epigenetic and transcriptional suppression of TLR9.
  • The E7 oncoprotein plays a critical role in orchestrating this suppression.
  • Targeting TLR9 impacts the host's interferon-mediated antiviral defense.

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