NF-κB-DRIVEN REPRESSION OF NRF2 FACILITATES HSV-1 REPLICATION IN SH-SY5Y NEUROBLASTOMA AND HeLa EPITHELIAL CELLS.

Authors

Eduardo I Tognarelli, Daniel A Cornejo, Exequiel J Del Campo, Rodrigo Reyes-Ramírez, Gerardo E Ortiz, Aracelly Gaete-Argel, Alexis M Kalergis, Susan M Bueno, Leandro J Carreño, Ricardo Soto-Rifo, Pablo A González

Published in

Antiviral research. Pages 106545. Sep 29, 2026. Epub Sep 29, 2026.

Abstract

Herpes simplex virus type 1 (HSV-1) can infect numerous cell types, including epithelial, neuronal, and immune cells, with varying cellular and disease outcomes. A common effect reported in HSV-1-infected cells is the early activation of the transcription factor nuclear factor kappa B (NF-κB), which is proposed to be a key factor for its replication. On the other hand, pharmacological induction of host heme oxygenase 1 (HO-1) expression, an effector of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway that regulates oxidative stress responses, has significant antiviral effects on HSV-1 replication. Because NF-κB and Nrf2 negatively co-regulate each other, we sought to determine the dynamics and interplay between these two pathways during HSV-1 infection in human neuroblastoma (SH-SY5Y) and epithelial (HeLa) cells. NF-κB inhibition or Nrf2 activation reduced HSV-1 replication in these cells, and activating or inhibiting either signaling pathway modulated the other. Notably, simultaneous inhibition of both NF-κB and Nrf2 activity, or of the HO-1 effector, fully restored viral output and viral protein expression in infected cells to control levels. This finding suggests that HSV-1 replication relies on NF-κB activation in these cells to inhibit the antiviral effects of the Nrf2 pathway. Additionally, we measured the kinetics of reactive oxygen species (ROS) production during infection to assess their relationship with NF-κB or Nrf2 activation and observed that ROS contributed to NF-κB activation and basal Nrf2 activity in infected cells. Overall, this study highlights a relevant interplay between NF-κB and Nrf2 during HSV-1 infection.

PMID:
42810523
Bibliographic data and abstract were imported from PubMed on 30 Sep 2026.

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