ArticleProceedings of the National Academy of Sciences of the United States of America2012
Nuclear IFI16 induction of IRF-3 signaling during herpesviral infection and degradation of IFI16 by the viral ICP0 protein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 311 papers.
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Who cites it
311 citing papers in PubMed, 416 citations in OpenAlex.
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- Immune Evasion by Neurotropic Viruses: Molecular Strategies, Cellular Targets, and Consequences for CNS Infection.International journal of molecular sciences · 2026Review
- Epithelial interferon-γ responsiveness shapes chemokine induction and clinical outcomes in herpes simplex virus infection.PLoS pathogens · 2026Article
- Expulsion of nuclear DNA to the cytoplasm after viral entry: A mechanism for activation of the cGAS pathway.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
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- IFI16 restricts SARS-CoV-2 replication by disrupting nucleocapsid-driven phase separation.Communications biology · 2026Article
- SUMOylation and ubiquitination reciprocally regulate SMCHD1 antiviral activity against herpes simplex virus 1.PLoS pathogens · 2026Article
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- HSV-2 genome recognition by nuclear cGAS instigates IFN-β production and influences inflammasome activation duringFrontiers in immunology · 2026Article
- Chromatin Regulation of HSV Gene Transcription.Viruses · 2025Review
- Latent Human Cytomegalovirus Infection Activates the STING Pathway but p-IRF3 Translocation Is Limited.Viruses · 2025Article
- IRF1 amplifies HSV-1-triggered antiviral innate immunity in a feed-forward manner.Cell insight · 2025Article
- Molecular mechanisms of co-infections.EMBO reports · 2025Review
- Sequestration of ribosome biogenesis factors in HSV-1 nuclear aggregates revealed by spatially resolved thermal profiling.Science advances · 2025Article
- Direct relationship between protein expression and progeny yield of herpes simplex virus 1.mBio · 2025Article
- Next-generation replication-defective HSV vectors for delivery of large DNA payloads.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
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- Herpes simplex virus 1 encodes a STING antagonist that can be therapeutically targeted.Cell reports. Medicine · 2025Article
- The role of NJournal of virology · 2025Review
251 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Innate sensing of microbial components is well documented to occur at many cellular sites, including at the cell surface, in the cytosol, and in intracellular vesicles, but there is limited evidence of nuclear innate signaling. In this study we have defined the mechanisms of interferon regulatory factor-3 (IRF-3) signaling in primary human foreskin fibroblasts (HFF) infected with herpes simplex virus 1 (HSV-1) in the absence of viral gene expression. We found that the interferon inducible protein 16 (IFI16) DNA sensor, which is required for induction of IRF-3 signaling in these cells, is nuclear, and its localization does not change detectably upon HSV-1 d109 infection and induction of IRF-3 signaling. Consistent with the IFI16 sensor being nuclear, conditions that block viral DNA release from incoming capsids inhibit IRF-3 signaling. An unknown factor must be exported from the nucleus to activate IRF-3 through cytoplasmic STING, which is required for IRF-3 activation and signaling. However, when the viral ICP0 protein is expressed in the nucleus, it causes the nuclear relocalization and degradation of IFI16, inhibiting IRF-3 signaling. Therefore, HSV-1 infection is sensed in HFF by nuclear IFI16 upon release of encapsidated viral DNA into the nucleus, and the viral nuclear ICP0 protein can inhibit the process by targeting IFI16 for degradation. Together these results define a pathway for nuclear innate sensing of HSV DNA by IFI16 in infected HFF and document a mechanism by which a virus can block this nuclear innate response.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.