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The Dual Role of Nrf2 Signaling in Virus Infections: Antiviral Guardian or Proviral Accomplice?

Bikash R Sahoo1,2, Kush K Pandey1,2, Asit K Pattnaik1,2

  • 1School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.

Pathogens (Basel, Switzerland)
|January 28, 2026
PubMed

Insights

The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) has dual roles in viral infections, acting as both a host defense activator and a tool exploited by viruses. Understanding these complex interactions is key for developing targeted antiviral therapies.

Area of Science:

  • Molecular Biology
  • Immunology
  • Virology

Background:

  • Nuclear factor erythroid 2-related factor 2 (Nrf2) is crucial for managing oxidative stress and redox balance.
  • Nrf2 signaling presents a complex role in viral infections, exhibiting both protective and detrimental effects.

Purpose of the Study:

  • To review the dual antiviral and proviral functions of Nrf2 in RNA and DNA virus infections.
  • To elucidate the mechanisms underlying Nrf2's involvement in viral pathogenesis.
  • To discuss the therapeutic potential of modulating Nrf2 for antiviral strategies.

Main Methods:

  • Literature review of studies on Nrf2 and viral infections.
  • Analysis of Nrf2's role in host defense and viral replication.
  • Synthesis of information on therapeutic targeting of Nrf2.

Main Results:

  • Nrf2 activates antioxidant and cytoprotective genes, supporting host antiviral immunity.
  • Some viruses hijack Nrf2 to promote their replication, persistence, or immune evasion.
  • Nrf2's impact varies depending on the specific virus and host context.

Conclusions:

  • Nrf2 acts as a double-edged sword in viral infections.
  • Targeting Nrf2 requires context-specific strategies for effective antiviral therapy.
  • Further research is needed to refine precision antiviral approaches based on Nrf2 modulation.
Keywords:
Keap1Nrf2antiviral immunityoxidative stressvirus infections

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