ArticleMolecular systems biology2015
The functional interactome of PYHIN immune regulators reveals IFIX is a sensor of viral DNA.
Article in Molecular systems biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
65 citing papers in PubMed, 89 citations in OpenAlex.
- PYHIN proteins: guardians or contributors to hepatitis B virus pathogenesis?Frontiers in immunology · 2026Review
- Structural insights into the atypical filament assembly of pyrin domain-containing IFI16.The EMBO journal · 2025Article
- Insights into Noncanonical and Diversified Functions of ABCF1: From Health to Disease.Journal of molecular biology · 2025Review
- IFI16 recruits HDAC1 and HDAC2 to deacetylate the Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA), facilitating latency.Journal of virology · 2025Article
- Catch me if you can: viral nucleic acids to host sensors.Frontiers in immunology · 2025Review
- Review
- When DNA-damage responses meet innate and adaptive immunity.Cellular and molecular life sciences : CMLS · 2024Review
- MNDA, a PYHIN factor involved in transcriptional regulation and apoptosis control in leukocytes.Frontiers in immunology · 2024Review
- Intrinsic disorder in flaviviral capsid proteins and its role in pathogenesis.Journal of biosciences · 2024Article
- IFI16 phase separation via multi-phosphorylation drives innate immune signaling.Nucleic acids research · 2023Article
- The Role of ATP-Binding Cassette Proteins in Stem Cell Pluripotency.Biomedicines · 2023Review
- Sirt1 Negatively Regulates Cellular Antiviral Responses by Preventing the Cytoplasmic Translocation of Interferon-Inducible Protein 16 in Human Cells.Journal of virology · 2023Article
- Interplay between RNA viruses and cGAS/STING axis in innate immunity.Frontiers in cellular and infection microbiology · 2023Review
- Pattern-recognition receptors in endometriosis: A narrative review.Frontiers in immunology · 2023Review
- Cytosolic DNA sensors and glial responses to endogenous DNA.Frontiers in immunology · 2023Review
- Nuclear antiviral innate responses at the intersection of DNA sensing and DNA repair.Trends in microbiology · 2022Review
- Interferon activated gene 204 protects against bone loss in experimental periodontitis.Journal of periodontology · 2022Article
- The Nuclear DNA Sensor IFI16 Indiscriminately Binds to and Diminishes Accessibility of the HSV-1 Genome to Suppress Infection.mSystems · 2022Article
- The Interplay between Viruses and Host DNA Sensors.Viruses · 2022Review
- Functions and roles of IFIX, a member of the human HIN-200 family, in human diseases.Molecular and cellular biochemistry · 2022Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The human PYHIN proteins, AIM2, IFI16, IFIX, and MNDA, are critical regulators of immune response, transcription, apoptosis, and cell cycle. However, their protein interactions and underlying mechanisms remain largely uncharacterized. Here, we provide the interaction network for all PYHIN proteins and define a function in sensing of viral DNA for the previously uncharacterized IFIX protein. By designing a cell-based inducible system and integrating microscopy, immunoaffinity capture, quantitative mass spectrometry, and bioinformatics, we identify over 300 PYHIN interactions reflective of diverse functions, including DNA damage response, transcription regulation, intracellular signaling, and antiviral response. In view of the IFIX interaction with antiviral factors, including nuclear PML bodies, we further characterize IFIX and demonstrate its function in restricting herpesvirus replication. We discover that IFIX detects viral DNA in both the nucleus and cytoplasm, binding foreign DNA via its HIN domain in a sequence-non-specific manner. Furthermore, IFIX contributes to the induction of interferon response. Our results highlight the value of integrative proteomics in deducing protein function and establish IFIX as an antiviral DNA sensor important for mounting immune responses.
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Registered trials
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.