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Updated: May 12, 2025

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
08:32

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production

Published on: March 2, 2014

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Human papillomavirus E1 proteins inhibit RIG-I/MDA5-MAVS, TLR3-TRIF, cGAS-STING, and JAK-STAT signaling pathways to

Jin-Xin Li1, Jing Zhang1, Cheng-Hao Li2

  • 1Department of Infectious Disease and Hepatology, The Second Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Frontiers in Immunology
|May 7, 2025
PubMed

Insights

Human papillomavirus E1 protein suppresses key antiviral signaling pathways, including interferon production. This immune evasion mechanism highlights E1 as a potential therapeutic target for HPV-associated diseases.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Human papillomavirus (HPV) causes benign and malignant lesions.
  • High-risk HPV types (e.g., HPV16, HPV18) are linked to cervical cancer.
  • HPV E6 and E7 proteins are known for immune evasion, but E1's role is unclear.

Purpose of the Study:

  • Investigate the immunomodulatory functions of HPV16 and HPV11 E1 proteins.
  • Determine how E1 affects host innate antiviral immune signaling pathways.
  • Characterize E1's role in viral immune evasion.

Main Methods:

  • RT-qPCR to measure gene expression.
  • Luciferase reporter assays to assess pathway activation.
  • Co-immunoprecipitation to identify protein interactions.

Main Results:

  • HPV E1 suppresses interferon and interferon-stimulated gene production.
  • E1 inhibits RIG-I/MDA5-MAVS, TLR3-TRIF, cGAS-STING, and JAK-STAT pathways.
  • E1 interacts with signaling molecules, impairs IRF3 phosphorylation, and blocks its nuclear translocation.
  • E1 disrupts the JAK-STAT pathway by binding STAT1, preventing ISGF3 complex formation.

Conclusions:

  • HPV E1 is a significant regulator of immune evasion by suppressing innate antiviral responses.
  • E1 targets multiple key signaling pathways, including interferon and JAK-STAT.
  • E1 represents a potential therapeutic target for enhancing antiviral immunity in HPV infections.
Keywords:
HPV E1JAK-STATRIG-I/MDA5-MAVScGAS-STINGimmune evasioninnate immunityinterferon

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