2. Academic Validation
  3. IRF1 amplifies HSV-1-triggered antiviral innate immunity in a feed-forward manner

IRF1 amplifies HSV-1-triggered antiviral innate immunity in a feed-forward manner

  • Cell Insight. 2025 May 22;4(4):100255. doi: 10.1016/j.cellin.2025.100255.
Ming Gao 1 2 3,  Yining Qi 1 2 3,  Junjie Zhang 1 2 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, State Key Laboratory of Virology and Biosafety, Medical Research Institute, Wuhan University, Wuhan 430071, Hubei, China.
  • 2 Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan 430071, Hubei, China.
  • 3 Hubei Key Laboratory of Tumor Biological Behavior, Hubei Province Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China.
PMID: 40586041 DOI: 10.1016/j.cellin.2025.100255
Abstract

Herpes simplex virus 1 (HSV-1) is a prevalent human pathogen that establishes lifelong Infection and causes a wide range of diseases. Antiviral innate immunity is critical for controlling HSV-1 replication; however, how host cells elicit a full spectrum of Antiviral innate immune responses against HSV-1 remains poorly understood. Here, our studies indicate that Interferon regulatory factor 1 (IRF1) amplifies HSV-1-induced Antiviral innate immunity in a feed-forward manner. Our data reveal that HSV-1 Infection induces IRF1 expression, and MITA/STING contributes to the induction of IRF1 during HSV-1 Infection. Moreover, IRF1 restricts HSV-1 replication dependent on its DNA-binding activity. Knockout of IRF1 significantly diminishes the induction of a large subset of interferon-stimulated genes (ISGs) critical for Antiviral defense during HSV-1 Infection. Notably, IRF1 interacts with IRF3, promoting its recruitment to the promoters of ISGs as well as type I and III interferons, thereby facilitating the activation of Antiviral signaling. These findings uncover a novel amplifying role of IRF1 in HSV-1-induced Antiviral immunity, which deepens our understanding of innate immune responses against viral infections.

Keywords

Antiviral innate immunity; HSV-1; IRF1; IRF3; MITA; STING.

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