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Updated: Dec 23, 2025

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
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Subversion of Host Innate Immunity by Human Papillomavirus Oncoproteins

Irene Lo Cigno1, Federica Calati1, Silvia Albertini1

  • 1Molecular Virology Unit, Department of Translational Medicine, Medical School, University of Piemonte Orientale, 28100 Novara, Italy.

Pathogens (Basel, Switzerland)
|April 23, 2020
PubMed

Insights

Human papillomavirus (HPV) oncoproteins E6/E7 suppress innate immunity. Inhibiting E6/E7 reactivates immune responses, offering a promising strategy for treating HPV-associated cancers by restoring immune function.

Area of Science:

  • Immunology
  • Virology
  • Oncology

Background:

  • Human papillomavirus (HPV) oncoproteins E6 and E7 drive cancer by suppressing host cell signaling pathways.
  • High-risk HPV types (e.g., HPV16/18) are particularly adept at immune evasion, facilitating viral persistence and tumor development.
  • Understanding how E6/E7 manipulate innate immunity is crucial for developing effective cancer therapies.

Purpose of the Study:

  • To review the current literature on the interaction between HPV E6/E7 oncoproteins and innate immune signaling pathways.
  • To elucidate the mechanisms by which E6/E7 disrupt immune surveillance in HPV-transformed cells.
  • To identify potential therapeutic targets for restoring innate immunity in HPV-associated cancers.

Main Methods:

  • Literature review of recent studies on HPV E6/E7 and innate immunity.
  • Analysis of the impact of E6/E7 on cGAS/STING/TBK1, RIG-I/MAVS/TBK1, and Toll-like receptor (TLR) pathways.
  • Examination of how E6/E7 mediate immune evasion and cancer progression.

Main Results:

  • HPV E6/E7 employ broad-spectrum mechanisms to inhibit multiple innate immune effectors simultaneously.
  • The cGAS/STING/TBK1 pathway is significantly impacted by E6/E7.
  • The RIG-I/MAVS/TBK1 pathway remains partially functional and can be activated by agonists like M8, leading to interferon production and enhanced chemotherapy efficacy.

Conclusions:

  • HPV E6/E7 actively suppress host innate immune responses through multifaceted strategies.
  • Targeting these immune evasion mechanisms, particularly by restoring RIG-I pathway function, holds therapeutic potential.
  • Developing novel therapies to reactivate innate immunity in HPV-transformed cells could revolutionize HPV-associated cancer treatment.
Keywords:
E6 and E7 oncoproteinsHPVHPV-driven cancerPRRhuman papillomavirusinnate immunitypathogen recognition receptors

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