ArticleFrontiers in immunology2018
Phosphorylation of TRIM28 Enhances the Expression of IFN-β and Proinflammatory Cytokines During HPAIV Infection of Human Lung Epithelial Cells.
Article in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 88 citations in OpenAlex.
- Human Influenza Virus Infection: A Focus on Key Host Determinants Linked to Clinical Disease Severity.Viruses · 2026Review
- TRIM47: molecular characteristics, disease-related mechanisms, and clinical translational value.Frontiers in immunology · 2026Review
- Updates on the role of TRIM proteins in AIDS: molecular mechanisms and potential for interventions.Frontiers in immunology · 2026Review
- Derepression of transposable elements in the mouse prefrontal cortex disrupts social behavior.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Identification of a lipid oxygen radical defense pathway and its epigenetic control.Nature communications · 2025Article
- TRIM28 is a target for paramyxovirus V proteins.PLoS pathogens · 2025Article
- Insights into the protein domains of C-VI TRIM subfamily in viral infection.Frontiers in cellular and infection microbiology · 2025Review
- KAP1 in antiviral immunity: dual roles in viral silencing and immune regulation.Frontiers in cellular and infection microbiology · 2025Review
- Enhanced Transcription of Human Endogenous Retroviruses and TRIM28 Downregulation in Patients with Inflammatory Bowel Disease.Viruses · 2024Article
- Structures of influenza A and B replication complexes give insight into avian to human host adaptation and reveal a role of ANP32 as an electrostatic chaperone for the apo-polymerase.Nature communications · 2024Article
- Genome-scale CRISPR-Cas9 screen identifies host factors as potential therapeutic targets for SARS-CoV-2 infection.iScience · 2024Article
- The host RNA polymerase II C-terminal domain is the anchor for replication of the influenza virus genome.Nature communications · 2024Article
- The Immune Modulatory Role of TIF1 Proteins.Advances in experimental medicine and biology · 2024Review
- Exploring TRIM proteins' role in antiviral defense against influenza A virus and respiratory coronaviruses.Frontiers in cellular and infection microbiology · 2024Review
- TRIM28 facilitates type I interferon activation by targeting TBK1.Frontiers in immunology · 2024Article
- Immune-epithelial cell cross-talk enhances antiviral responsiveness to SARS-CoV-2 in children.EMBO reports · 2023Article
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- Acetylation-Mimic Mutation of TRIM28-Lys304 to Gln Attenuates the Interaction with KRAB-Zinc-Finger Proteins and Affects Gene Expression in Leukemic K562 Cells.International journal of molecular sciences · 2023Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human infection with highly pathogenic avian influenza viruses (HPAIV) is often associated with severe tissue damage due to hyperinduction of interferons and proinflammatory cytokines. The reasons for this excessive cytokine expression are still incompletely understood, which has hampered the development of efficient immunomodulatory treatment options. The host protein TRIM28 associates to the promoter regions of over 13,000 genes and is recognized as a genomic corepressor and negative immune regulator. TRIM28 corepressor activity is regulated by post-translational modifications, specifically phosphorylation of S473, which modulates binding of TRIM28 to the heterochromatin-binding protein HP1. Here, we identified TRIM28 as a key immune regulator leading to increased IFN-β and proinflammatory cytokine levels during infection with HPAIV. Using influenza A virus strains of the subtype H1N1 as well as HPAIV of subtypes H7N7, H7N9, and H5N1, we could demonstrate that strain-specific phosphorylation of TRIM28 S473 is induced by a signaling cascade constituted of PKR, p38 MAPK, and MSK1 in response to RIG-I independent sensing of viral RNA. Furthermore, using chemical inhibitors as well as knockout cell lines, our results suggest that phosphorylation of S473 facilitates a functional switch leading to increased levels of IFN-β, IL-6, and IL-8. In summary, we have identified TRIM28 as a critical factor controlling excessive expression of type I IFNs as well as proinflammatory cytokines during infection with H5N1, H7N7, and H7N9 HPAIV. In addition, our data indicate a novel mechanism of PKR-mediated IFN-β expression, which could lay the ground for novel treatment options aiming at rebalancing dysregulated immune responses during severe HPAIV infection.
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