Work

A range of NRF2-driven restriction factors inhibit Hepatitis C virus replication

Year: 2026

Type: article

Abstract: The transcription factor NRF2 (Nuclear factor erythroid 2-related factor 2) has recently emerged as an important component in non-canonical anti-viral immunity. We have previously reported that NRF2 agonists induce a distinct interferon (IFN)-independent antiviral program that is broadly effective in limiting virus replication of human pathogenic viruses, including SARS-CoV-2. Using both live infectious virus as well as a subgenomic replicon system, we demonstrate that CRISPR-mediated induction of endogenous NRF2 expression restricted Hepatitis C virus (HCV) replication. Further, using a focused CRISPR-activation (CRISPRa) screen, we pinpoint a broad range of NRF2-driven antiviral effector genes each of which restricted HCV replication. Importantly, we identified the RNA-binding protein ZC3H12C to have potent antiviral effects across assays, suggesting that this factor is an important antiviral effector of NRF2. In conclusion, we demonstrate that NRF2 controls a range of restriction factors that can limit HCV replication and identify ZC3H12C as a novel anti-viral effector gene.

Source: Advances in Redox Research

DOI: 10.1016/j.arres.2026.100206