ArticleNature microbiology2022
Dual inhibition of innate immunity and apoptosis by human cytomegalovirus protein UL37x1 enables efficient virus replication.
Article in Nature microbiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 53 citations in OpenAlex.
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.Signal transduction and targeted therapy · 2026Review
- The cGAS-STING pathway: mechanistic basis, dual biological functions and translational therapeutic advances.Apoptosis : an international journal on programmed cell death · 2026Review
- Regulatory NLRs in HSV-1 Infection: Direct Evidence, Comparative Mechanisms and Testable Hypotheses.Pathogens (Basel, Switzerland) · 2026Review
- Detangling knots: the intricate roles of G-quadruplexes in herpesvirus replication.Journal of virology · 2026Review
- Alpha-herpesvirus UL55 synergizes with ICP27 to suppress type I interferon production through conserved and host-adapted mechanisms.Journal of virology · 2026Article
- HCMV-pUS2 Disrupts cGAS-STING Signaling through LMAN2L Degradation.PLoS pathogens · 2026Article
- Non-viral targeted integration of large DNA in primary human T cells independent of double-stranded DNA breaks.Nature biomedical engineering · 2026Article
- The cGAS-STING pathway at the crossroads of neuroimmunology: bridging innate immunity to aging and neurodegeneration.Biomarker research · 2026Review
- The cGAS-STING pathway in fibroblast microenvironment: from molecular mechanisms to targeted therapies.Apoptosis : an international journal on programmed cell death · 2026Review
- Identification of extracellular vesicle microRNAs as potential facilitators of interferon-alpha escape in Marek's disease virus infection.Frontiers in cellular and infection microbiology · 2026Article
- Cellular sensor DAP5 decodesFrontiers in immunology · 2026Article
- cGAS-STING signaling pathway as a therapeutic target in human diseases.Chinese medical journal · 2025Review
- Does human cytomegalovirus provide a novel therapeutic target for patients with glioblastoma?Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- The tegument protein VP22 of pseudorabies virus inhibits cGAS condensation by inducing nuclear-to-cytoplasmic translocation of DDX21.PLoS pathogens · 2025Article
- Global cis-regulatory landscape of double-stranded DNA viruses.bioRxiv : the preprint server for biology · 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
- Zika virus inhibits cell death by inhibiting the expression of NLRP3 and A20.Journal of virology · 2025Article
- SARS-CoV-2-ORF-3a Mediates Apoptosis Through Mitochondrial Dysfunction Modulated by the KInternational journal of molecular sciences · 2025Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune evasion and inhibition of apoptosis are required for successful virus infection. However, inhibition of apoptosis can increase antiviral immune responses, which can then clear viral infections. Here we show that human cytomegalovirus (HCMV)-encoded UL37 exon-1 protein (UL37x1) not only inhibits apoptosis but also suppresses the cGAS-STING immune pathway. Using co-immunoprecipitation assays, we found that UL37x1 binds to TBK1 to abrogate the TBK1-STING-IRF3 interaction. Although the anti-apoptosis function of UL37x1 increases immune signalling, the immunosuppressive role of UL37x1 counteracts this undesirable side-effect. Furthermore, we used mutational analyses to show that the loss of either immunosuppressive or anti-apoptotic function of UL37x1 significantly reduced HCMV replication in human primary foreskin fibroblasts and humanized mice by over twofold. Finally, loss of both functions resulted in over fourfold reduction of HCMV replication in the same cell type and mouse model, showing that both UL37x1 functions are crucial for HCMV infection. We conclude that this sophisticated mechanism enables HCMV to control innate immunity and apoptosis to ensure efficient 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 Socratic graph.