ArticleRetrovirology2014
dNTP pool modulation dynamics by SAMHD1 protein in monocyte-derived macrophages.
Article in Retrovirology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- SAMHD1 shapes deoxynucleotide triphosphate homeostasis by interconnecting the depletion and biosynthesis of different dNTPs.Nature communications · 2025Article
- Removal of innate immune barriers allows efficient transduction of quiescent human hematopoietic stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Replication-competent HIV-1 in human alveolar macrophages and monocytes despite nucleotide pools with elevated dUTP.Retrovirology · 2022Article
- Molecular Biology and Diversification of Human Retroviruses.Frontiers in virology (Lausanne, Switzerland) · 2022Article
- Enhanced enzyme kinetics of reverse transcriptase variants cloned from animals infected with SIVmac239 lacking viral protein X.The Journal of biological chemistry · 2020Article
- Neutrophil extracellular traps from healthy donors and HIV-1-infected individuals restrict HIV-1 production in macrophages.Scientific reports · 2020Article
- SAMHD1 Functions and Human Diseases.Viruses · 2020Review
- Viral protein X reduces the incorporation of mutagenic noncanonical rNTPs during lentivirus reverse transcription in macrophages.The Journal of biological chemistry · 2020Article
- Degradation of SAMHD1 Restriction Factor Through Cullin-Ring E3 Ligase Complexes During Human Cytomegalovirus Infection.Frontiers in cellular and infection microbiology · 2020Article
- Human cytomegalovirus overcomes SAMHD1 restriction in macrophages via pUL97.Nature microbiology · 2019Article
- Effect of induced dNTP pool imbalance on HIV-1 reverse transcription in macrophages.Retrovirology · 2019Article
- A Novel Mechanism Driving Poor-Prognosis Prostate Cancer: Overexpression of the DNA Repair Gene, Ribonucleotide Reductase Small Subunit M2 (RRM2).Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Detailed Characterization of Early HIV-1 Replication Dynamics in Primary Human Macrophages.Viruses · 2018Article
- Host SAMHD1 protein restricts endogenous reverse transcription of HIV-1 in nondividing macrophages.Retrovirology · 2018Article
- SAMHD1: Recurring roles in cell cycle, viral restriction, cancer, and innate immunity.Autoimmunity · 2018Review
- Substrates and Inhibitors of SAMHD1.PloS one · 2017Article
- Metabolism, Biochemical Actions, and Chemical Synthesis of Anticancer Nucleosides, Nucleotides, and Base Analogs.Chemical reviews · 2016Review
- Allosteric Activation of SAMHD1 Protein by Deoxynucleotide Triphosphate (dNTP)-dependent Tetramerization Requires dNTP Concentrations That Are Similar to dNTP Concentrations Observed in Cycling T Cells.The Journal of biological chemistry · 2016Article
- Article
- Macrophages in Progressive Human Immunodeficiency Virus/Simian Immunodeficiency Virus Infections.Journal of virology · 2016Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundSAMHD1 degrades deoxyribonucleotides (dNTPs), suppressing viral DNA synthesis in macrophages. Recently, viral protein X (Vpx) of HIV-2/SIVsm was shown to target SAMHD1 for proteosomal degradation and led to elevation of dNTP levels, which in turn accelerated proviral DNA synthesis of lentiviruses in macrophages.
resultsWe investigated both time-dependent and quantitative interplays between SAMHD1 level and dNTP concentrations during multiple exposures of Vpx in macrophages. The following were observed. First, SAMHD1 level was rapidly reduced by Vpx + VLP to undetectable levels by Western blot analysis. Recovery of SAMHD1 was very slow with less than 3% of the normal macrophage level detected at day 6 post Vpx treatment and only ~30% recovered at day 14. Second, dGTP, dCTP and dTTP levels peaked at day 1 post Vpx treatment, whereas dATP peaked at day 2. However, all dNTPs rapidly decreased starting at day 3, while SAMHD1 level was below the level of detection. Third, when Vpx pretreated macrophages were re-exposed to a second Vpx treatment at day 7, we observed dNTP elevation that had faster kinetics than the first Vpx + VLP treatment. Moreover, we performed a short kinetic analysis of the second Vpx treatment to find that dATP and dGTP levels peaked at 8 hours post secondary VLP treatment. dGTP peak was consistently higher than the primary, whereas peak dATP concentration was basically equivalent to the first Vpx + VLP treatment. Lastly, HIV-1 replication kinetics were faster in macrophages treated after the secondary Vpx treatments when compared to the initial single Vpx treatment.
conclusionThis study reveals that a very low level of SAMHD1 sufficiently modulates the normally low dNTP levels in macrophages and proposes potential diverse mechanisms of Vpx-mediated dNTP regulation in macrophages.
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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.