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

TL;DR

This paper explores how a key cellular factor, Nrf2, can both protect against and aid viruses, depending on the context of infection.

Contribution

The paper provides a comprehensive review of Nrf2's dual role in viral infections, highlighting its antiviral and proviral functions.

Findings

Nrf2 signaling can enhance host defense by activating antioxidant and cytoprotective genes.

Some viruses exploit Nrf2 to promote their replication and immune evasion.

Context-dependent modulation of Nrf2 is crucial for effective antiviral therapies.

Abstract

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in regulating cellular defense against oxidative stress and maintaining redox homeostasis. In the context of viral infections, Nrf2 signaling emerges as a double-edged sword. On one hand, it activates a broad spectrum of antioxidant and cytoprotective genes, contributing to host defense and antiviral immunity. On the other hand, certain viruses exploit the Nrf2 pathway to create a favorable environment for replication, persistence, or immune evasion. This review summarizes the current understanding of Nrf2’s antiviral and proviral roles in both RNA and DNA virus infections, delineates the underlying mechanisms, and discusses the therapeutic implications of targeting Nrf2. We emphasize the need for context-dependent modulation of Nrf2 activity and highlight future directions in precision antiviral strategies.

Figures