ArticleThe Journal of biological chemistry2013
Anti-HIV host factor SAMHD1 regulates viral sensitivity to nucleoside reverse transcriptase inhibitors via modulation of cellular deoxyribonucleoside triphosphate (dNTP) levels.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 53 citations in OpenAlex.
- Nucleotide Metabolism in Health and Disease.MedComm · 2026Review
- Continuous assay for the dNTP triphosphohydrolase of activated SAMHD1.Analytical biochemistry · 2026Article
- Structural and functional relevance of the DUF4352 domain in antiviral immunity and physiology of mycobacteria.Nucleic acids research · 2025Article
- Platform-directed allostery and quaternary structure dynamics of SAMHD1 catalysis.Nature communications · 2024Article
- Review
- Probing the Catalytic Mechanism and Inhibition of SAMHD1 Using the Differential Properties of RBiochemistry · 2021Article
- SAMHD1 … and Viral Ways around It.Viruses · 2021Review
- SAMHD1 is a key regulator of the lineage-specific response of acute lymphoblastic leukaemias to nelarabine.Communications biology · 2020Article
- Crystal structures of SAMHD1 inhibitor complexes reveal the mechanism of water-mediated dNTP hydrolysis.Nature communications · 2020Article
- SAMHD1 Functions and Human Diseases.Viruses · 2020Review
- Pharmacological Modulation of SAMHD1 Activity by CDK4/6 Inhibitors Improves Anticancer Therapy.Cancers · 2020Article
- Single-molecule detection of deoxyribonucleoside triphosphates in microdroplets.Nucleic acids research · 2019Article
- The missing link: allostery and catalysis in the anti-viral protein SAMHD1.Biochemical Society transactions · 2019Review
- Identification of Inhibitors of the dNTP Triphosphohydrolase SAMHD1 Using a Novel and Direct High-Throughput Assay.Biochemistry · 2018Article
- The structural basis for cancer drug interactions with the catalytic and allosteric sites of SAMHD1.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Observational
- SAMHD1: Recurring roles in cell cycle, viral restriction, cancer, and innate immunity.Autoimmunity · 2018Review
- Article
- Incomplete Suppression of HIV-1 by SAMHD1 Permits Efficient Macrophage Infection.Pathogens & immunity · 2018Article
- Fidelity of classwide-resistant HIV-2 reverse transcriptase and differential contribution of K65R to the accuracy of HIV-1 and HIV-2 reverse transcriptases.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Newly identified anti-HIV host factor, SAMHD1, restricts replication of lentiviruses such as HIV-1, HIV-2, and simian immunodeficiency virus in macrophages by enzymatically hydrolyzing and depleting cellular dNTPs, which are the substrates of viral DNA polymerases. HIV-2 and some simian immunodeficiency viruses express viral protein X (VPX), which counteracts SAMHD1 and elevates cellular dNTPs, enhancing viral replication in macrophages. Because nucleoside reverse transcriptase inhibitors (NRTIs), the most commonly used anti-HIV drugs, compete against cellular dNTPs for incorporation into proviral DNA, we tested whether SAMHD1 directly affects the efficacy of NRTIs in inhibiting HIV-1. We found that reduction of SAMHD1 levels with the use of virus-like particles expressing Vpx- and SAMHD1-specific shRNA subsequently elevates cellular dNTPs and significantly decreases HIV-1 sensitivity to various NRTIs in macrophages. However, virus-like particles +Vpx treatment of activated CD4(+) T cells only minimally reduced NRTI efficacy. Furthermore, with the use of HPLC, we could not detect SAMHD1-mediated hydrolysis of NRTI-triphosphates, verifying that the reduced sensitivity of HIV-1 to NRTIs upon SAMHD1 degradation is most likely caused by the elevation in cellular dNTPs.
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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.