IRF1 amplifies HSV-1-triggered antiviral innate immunity in a feed-forward manner
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 H...
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| Language: | English |
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Elsevier
2025-08-01
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| Series: | Cell Insight |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S277289272500029X |
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| author | Ming Gao Yining Qi Junjie Zhang |
| author_facet | Ming Gao Yining Qi Junjie Zhang |
| author_sort | Ming Gao |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d8ca5389248041dea3260ffe1a8a0519 |
| institution | Kabale University |
| issn | 2772-8927 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Insight |
| spelling | doaj-art-d8ca5389248041dea3260ffe1a8a05192025-08-20T03:33:06ZengElsevierCell Insight2772-89272025-08-014410025510.1016/j.cellin.2025.100255IRF1 amplifies HSV-1-triggered antiviral innate immunity in a feed-forward mannerMing Gao0Yining Qi1Junjie Zhang2State 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; Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan 430071, Hubei, China; Hubei Key Laboratory of Tumor Biological Behavior, Hubei Province Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, ChinaState 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; Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan 430071, Hubei, China; Hubei Key Laboratory of Tumor Biological Behavior, Hubei Province Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, ChinaState 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; Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan 430071, Hubei, China; Hubei Key Laboratory of Tumor Biological Behavior, Hubei Province Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China; Corresponding author. 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.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.http://www.sciencedirect.com/science/article/pii/S277289272500029XHSV-1IRF1MITASTINGAntiviral innate immunityIRF3 |
| spellingShingle | Ming Gao Yining Qi Junjie Zhang IRF1 amplifies HSV-1-triggered antiviral innate immunity in a feed-forward manner Cell Insight HSV-1 IRF1 MITA STING Antiviral innate immunity IRF3 |
| title | IRF1 amplifies HSV-1-triggered antiviral innate immunity in a feed-forward manner |
| title_full | IRF1 amplifies HSV-1-triggered antiviral innate immunity in a feed-forward manner |
| title_fullStr | IRF1 amplifies HSV-1-triggered antiviral innate immunity in a feed-forward manner |
| title_full_unstemmed | IRF1 amplifies HSV-1-triggered antiviral innate immunity in a feed-forward manner |
| title_short | IRF1 amplifies HSV-1-triggered antiviral innate immunity in a feed-forward manner |
| title_sort | irf1 amplifies hsv 1 triggered antiviral innate immunity in a feed forward manner |
| topic | HSV-1 IRF1 MITA STING Antiviral innate immunity IRF3 |
| url | http://www.sciencedirect.com/science/article/pii/S277289272500029X |
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