ArticleCell host & microbe2023
Pathogen-driven CRISPR screens identify TREX1 as a regulator of DNA self-sensing during influenza virus infection.
Article in Cell host & microbe, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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37 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Systematic review and meta-analysis of genome-wide pooled CRISPR screens to identify host factors involved in influenza A virus infection.Journal of virology · 2024Pooled it
- TRIM62 facilitates influenza A virus entry by regulating WASH-dependent endosomal trafficking.EMBO reports · 2026Article
- A functional genomics-pharmacotranscriptomics framework identifies host-directed anti-influenza agents.iScience · 2026Article
- Selective targeting of human TREX1 exonuclease by small molecule inhibitors is mediated by a conformational switch.NAR molecular medicine · 2026Article
- USP17L13 Enhances Influenza a Virus Replication by Mediating the Degradation of RIG-I and MDA5.Viruses · 2026Article
- Multidimensional analysis of host-virus interactions using the virus-encoded CRISPR-based direct readout system (VECOS).Nature protocols · 2026Review
- Fasting-mimicking diet induces IFNβ secretion in tumor-associated macrophages via NRF1-mediated ubiquitin-dependent proteolysis of Trex1.British journal of cancer · 2026Article
- Confronting the known unknown: historical lessons and future strategies for Disease X.Frontiers in public health · 2026Review
- Replicon-based genome-wide CRISPR knockout screening for the identification of host factors involved in viral replication.Nature communications · 2025Article
- Mitochondrial targeting by measles virus nucleoprotein modulates viral spread in human airway epithelium.PLoS pathogens · 2025Article
- Gigaxonin Potentiates Antiviral Innate Immune Responses by Targeting cGAS and TREX1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Replication-competent adenovirus reporters utilizing endogenous viral expression architecture.Journal of virology · 2025Article
- CRISPR with Transcriptional Readout reveals influenza transcription is modulated by NELF and can precipitate an interferon response.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- IFIT3 RNA-binding activity promotes influenza A virus infection and translation efficiency.Journal of virology · 2025Article
- SARS-CoV-2 infection induces ZBP1-dependent PANoptosis in bystander cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The impact ofCellular and molecular life sciences : CMLS · 2025Article
- CRISPR with Transcriptional Readout reveals influenza transcription is modulated by NELF and can precipitate an interferon response.bioRxiv : the preprint server for biology · 2025Article
- Advancements in CRISPR/Cas systems for disease treatment.Acta pharmaceutica Sinica. B · 2025Review
- Deep mutational scanning and CRISPR-engineered viruses: tools for evolutionary and functional genomics studies.mSphere · 2025Review
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Authors and funding
11 authors at 2 institutions in 1 country.
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Abstract
Host:pathogen interactions dictate the outcome of infection, yet the limitations of current approaches leave large regions of this interface unexplored. Here, we develop a novel fitness-based screen that queries factors important during the middle to late stages of infection. This is achieved by engineering influenza virus to direct the screen by programming dCas9 to modulate host gene expression. Our genome-wide screen for pro-viral factors identifies the cytoplasmic DNA exonuclease TREX1. TREX1 degrades cytoplasmic DNA to prevent inappropriate innate immune activation by self-DNA. We reveal that this same process aids influenza virus replication. Infection triggers release of mitochondrial DNA into the cytoplasm, activating antiviral signaling via cGAS and STING. TREX1 metabolizes the DNA, preventing its sensing. Collectively, these data show that self-DNA is deployed to amplify innate immunity, a process tempered by TREX1. Moreover, they demonstrate the power and generality of pathogen-driven fitness-based screens to pinpoint key host regulators of infection.
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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.