ArticleProceedings of the National Academy of Sciences of the United States of America2018
SAMHD1 suppresses innate immune responses to viral infections and inflammatory stimuli by inhibiting the NF-κB and interferon pathways.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 1 of them a synthesis that pooled it.
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Who cites it
96 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- Disrupting Mechanisms that Regulate Genomic Repeat Elements to Combat Cancer and Drug Resistance.Frontiers in cell and developmental biology · 2022Pooled it
- Nanoparticle-based strategies targeting disulfidptosis, anoikis, and PANoptosis for enhanced cancer therapy.Journal of nanobiotechnology · 2026Review
- CNS1-dependent regulatory T cells shape recovery from acute lung injury.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Glycosylation as a dynamic regulator of RLR and cGAS-STING innate immune signalling pathways.Communications biology · 2026Review
- SAMHD1 depletion restricts SARS-CoV-2 infection by suppressing HNF1-dependent ACE2 expression in lung epithelial cells.PLoS pathogens · 2026Article
- SAMHD1 drives immunosuppression in non-small cell lung cancer by promoting macrophage infiltration and restricting oncolytic adenovirus replication.Journal for immunotherapy of cancer · 2026Article
- Nucleotide metabolic rewiring enables NLRP3 inflammasome hyperactivation in obesity.Science (New York, N.Y.) · 2026Article
- HIV-2 infection as a comparative lens for functional HIV-1 remission.Frontiers in immunology · 2026Review
- Glucocorticoid Receptor Activation Reprograms NK Cells to Drive AREG-Mediated Immunosuppression: A Pan-Cancer Role for AREG.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Continuous assay for the dNTP triphosphohydrolase of activated SAMHD1.Analytical biochemistry · 2026Article
- Selective depletion of tumor-associated SAMHD1 enhances chemotherapeutic efficacy and antitumor immune responses.Signal transduction and targeted therapy · 2025Article
- RNA and ChIP-sequencing analysis reveals SOX3 suppresses antiviral innate immunity through the AKT1-PTEN signaling axis.Virologica Sinica · 2025Article
- SAMHD1 promotes SARS-CoV-2 infection by enhancing HNF1-dependent ACE2 expression in lung epithelial cells.bioRxiv : the preprint server for biology · 2025Article
- SAMHD1 enhances HIV-1-induced apoptosis in monocytic cells via the mitochondrial pathway.mBio · 2025Article
- dNTP depletion and beyond: the multifaceted nature of SAMHD1-mediated viral restriction.Journal of virology · 2025Review
- Nuclear Overexpression of SAMHD1 Induces M Phase Stalling in Hepatoma Cells and Suppresses HCC Progression by Interacting with the Cohesin Complex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Hantaan virus glycoprotein Gc induces NEDD4-dependent PTEN ubiquitination and degradation to escape the restriction of autophagosomes and facilitate viral propagation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- SAMHD1 deficiency enhances macrophage-mediated clearance ofFrontiers in immunology · 2025Article
- The role of inflammatory gene polymorphisms in severe COVID-19: a review.Virology journal · 2024Review
- Aggravating mechanisms from COVID-19.Virology journal · 2024Review
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Sterile alpha motif and HD-domain-containing protein 1 (SAMHD1) blocks replication of retroviruses and certain DNA viruses by reducing the intracellular dNTP pool. SAMHD1 has been suggested to down-regulate IFN and inflammatory responses to viral infections, although the functions and mechanisms of SAMHD1 in modulating innate immunity remain unclear. Here, we show that SAMHD1 suppresses the innate immune responses to viral infections and inflammatory stimuli by inhibiting nuclear factor-κB (NF-κB) activation and type I interferon (IFN-I) induction. Compared with control cells, infection of SAMHD1-silenced human monocytic cells or primary macrophages with Sendai virus (SeV) or HIV-1, or treatment with inflammatory stimuli, induces significantly higher levels of NF-κB activation and IFN-I induction. Exogenous SAMHD1 expression in cells or SAMHD1 reconstitution in knockout cells suppresses NF-κB activation and IFN-I induction by SeV infection or inflammatory stimuli. Mechanistically, SAMHD1 inhibits NF-κB activation by interacting with NF-κB1/2 and reducing phosphorylation of the NF-κB inhibitory protein IκBα. SAMHD1 also interacts with the inhibitor-κB kinase ε (IKKε) and IFN regulatory factor 7 (IRF7), leading to the suppression of the IFN-I induction pathway by reducing IKKε-mediated IRF7 phosphorylation. Interactions of endogenous SAMHD1 with NF-κB and IFN-I pathway proteins were validated in human monocytic cells and primary macrophages. Comparing splenocytes from
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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.