ArticleScience advances2023
Human cytomegalovirus UL36 inhibits IRF3-dependent immune signaling to counterbalance its immunoenhancement as apoptotic inhibitor.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 15 citations in OpenAlex.
- Deletion of the N-terminal 400 amino acids of DPV pUL36 attenuated virulence and conferred effective protection against virulent challenge.Poultry science · 2026Article
- Non-viral targeted integration of large DNA in primary human T cells independent of double-stranded DNA breaks.Nature biomedical engineering · 2026Article
- Article
- Latent Human Cytomegalovirus Infection Activates the STING Pathway but p-IRF3 Translocation Is Limited.Viruses · 2025Article
- Targeting STING antagonism in HSV-1: A peptide-based strategy to restore antiviral immunity and suppress viral pathogenesis.Cell reports. Medicine · 2025Article
- Herpes simplex virus 1 encodes a STING antagonist that can be therapeutically targeted.Cell reports. Medicine · 2025Article
- Spatial Analysis of Placentae During Congenital Cytomegalovirus Infection Reveals Distinct Cellular Profiles in Immune Cells and Trophoblasts.bioRxiv : the preprint server for biology · 2025Article
- Herpes simplex virus-1 targets the 2'-3'cGAMP importer SLC19A1 as an antiviral countermeasure.Virology · 2025Article
- Recent advances in human cytomegalovirus: a comprehensive review of pathogenic mechanisms, virus-host interactions, and antiviral strategies.Frontiers in immunology · 2025Review
- Human cytomegalovirus: pathogenesis, prevention, and treatment.Molecular biomedicine · 2024Review
- Exploring the interaction mechanisms between cervical carcinoma in situ and antibody-mediated immune responses through Mendelian randomization analysis.Discover oncology · 2024Article
- Simultaneously Controlling Inflammation and Infection by Smart Nanomedicine Responding to the Inflammatory Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The battle between host antiviral innate immunity and immune evasion by cytomegalovirus.Cellular and molecular life sciences : CMLS · 2024Review
- Cytomegalovirus inhibitors of programmed cell death restrict antigen cross-presentation in the priming of antiviral CD8 T cells.PLoS pathogens · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apoptotic inhibition and immune evasion have particular importance to efficient viral infection, while a dilemma often faced by viruses is that inhibiting apoptosis can up-regulate antiviral immune signaling. Herein, we uncovered that in addition to inhibiting caspase-8/extrinsic apoptosis, human cytomegalovirus (HCMV)-encoded UL36 suppresses interferon regulatory factor 3 (IRF3)-dependent immune signaling by directly targeting IRF3 to abrogate IRF3 interaction with stimulator of interferon genes or TANK-binding kinase 1 and inhibit IRF3 phosphorylation/activation. Although UL36-mediated caspase-8/extrinsic apoptosis inhibition enhances immune signaling, the immunosuppressing activity of UL36 counterbalances this immunoenhancing "side effect" undesirable for virus. Furthermore, we used mutational analyses to show that only the wild-type, but not the UL36 mutant losing either inhibitory activity, is sufficient to support effective HCMV replication in cells, showing the functional importance of the dual inhibition by UL36 for the HCMV life cycle. Together, our findings demonstrate a sophisticated mechanism by which HCMV tightly controls innate immune signaling and extrinsic apoptosis for efficient infection.
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