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Updated: Jan 22, 2026
Arbovirus Infections As Screening Tools for the Identification of Viral Immunomodulators and Host Antiviral Factors
Published on: September 13, 2018
Nuclear factor erythroid 2-related factor: potential use as a therapeutic strategy for viral infections
Sama Akbarzadeh1,2, Javad Arabpour3, Zahra Yekanipour4
1Institute of Graduate Studies in Health Sciences, Istanbul University, Istanbul, Turkey.
Abstract:
Nuclear factor erythroid 2-related factor 2 (NRF2) is a central regulator of redox balance and innate antiviral defense. Because many viruses induce oxidative stress to support replication or evade immunity, understanding how NRF2 responds to infection is essential for identifying new therapeutic strategies. Current evidence shows that viral pathogens, ranging from respiratory viruses to hepatic, neurotropic, and retroviral infections, differentially manipulate the NRF2-Keap1 pathway. NRF2 activation can suppress viral replication, reduce oxidative damage, and limit inflammation, while certain viruses inhibit NRF2 to promote immune evasion or chronic disease. We also highlight situations in which persistent NRF2 activation supports cell survival and contributes to virus-associated carcinogenesis. We also demonstrate that NRF2-activating compounds such as sulforaphane, dimethyl fumarate, and 4-octyl-itaconate can modulate antiviral and anti-inflammatory responses. These insights identify NRF2 as a promising target for host-directed antiviral therapy. Disease-specific NRF2 activation or inhibition may enhance treatment efficacy, reduce tissue injury, and mitigate long-term complications. Therefore, understanding how viruses exploit or suppress NRF2 provides a basis for developing selective NRF2 modulators with translational potential for managing acute and chronic viral infections.
Insights
Nuclear factor erythroid 2-related factor 2 (NRF2) is key to antiviral defense. Manipulating NRF2 offers a promising therapeutic strategy for viral infections by modulating immune responses and reducing damage.
Area of Science:
- Molecular biology
- Immunology
- Virology
Background:
- Nuclear factor erythroid 2-related factor 2 (NRF2) is a crucial regulator of cellular redox balance and innate immune responses.
- Viruses often induce oxidative stress to facilitate replication or evade host immunity, making NRF2's role in infection critical.
- The NRF2-Keap1 pathway is differentially manipulated by various viral pathogens, impacting disease outcomes.
Purpose of the Study:
- To explore the multifaceted roles of NRF2 in viral infections.
- To investigate how viral pathogens interact with the NRF2-Keap1 pathway.
- To identify NRF2 as a potential therapeutic target for antiviral strategies.
Main Methods:
- Review and synthesis of current scientific literature on NRF2 and viral infections.
- Analysis of how viral manipulation of NRF2 affects viral replication, host immunity, and disease progression.
- Examination of the therapeutic potential of NRF2-activating compounds.
Main Results:
- Viral pathogens differentially manipulate the NRF2-Keap1 pathway, with varied consequences for viral replication and host defense.
- NRF2 activation can suppress viral replication, reduce oxidative stress, and limit inflammation.
- Conversely, some viruses inhibit NRF2 to promote immune evasion or chronic disease; persistent NRF2 activation may contribute to virus-associated carcinogenesis.
Conclusions:
- NRF2 is a promising target for host-directed antiviral therapies.
- Selective modulation of NRF2 activity (activation or inhibition) holds potential for enhancing treatment efficacy, reducing tissue injury, and mitigating long-term complications in viral infections.
- Understanding virus-specific NRF2 interactions is crucial for developing targeted NRF2 modulators for managing viral diseases.
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