ArticleThe Journal of biological chemistry2011
Abundant non-canonical dUTP found in primary human macrophages drives its frequent incorporation by HIV-1 reverse transcriptase.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Insights and progress on epidemic characteristics, pathogenesis, and preventive measures of African swine fever virus: A review.Virulence · 2025Review
- Review
- Replication-competent HIV-1 in human alveolar macrophages and monocytes despite nucleotide pools with elevated dUTP.Retrovirology · 2022Article
- Human Immunodeficiency Virus Type 1 Vpr Mediates Degradation of APC1, a Scaffolding Component of the Anaphase-Promoting Complex/Cyclosome.Journal of virology · 2021Article
- Genomic Uracil and Aberrant Profile of Demethylation Intermediates in Epigenetics and Hematologic Malignancies.International journal of molecular sciences · 2021Review
- Review
- Ribonucleotide reductase inhibitors suppress SAMHD1 ara-CTPase activity enhancing cytarabine efficacy.EMBO molecular medicine · 2020Article
- Deficient uracil base excision repair leads to persistent dUMP in HIV proviruses during infection of monocytes and macrophages.PloS one · 2020Article
- Article
- Genome-wide mapping of regions preferentially targeted by the human DNA-cytosine deaminase APOBEC3A using uracil-DNA pulldown and sequencing.The Journal of biological chemistry · 2019Article
- Deoxyuridine in DNA has an inhibitory and promutagenic effect on RNA transcription by diverse RNA polymerases.Nucleic acids research · 2019Article
- Illuminating the Role of Vpr in HIV Infection of Myeloid Cells.Frontiers in immunology · 2019Review
- HIV-1 Vpr Reprograms CLR4mBio · 2018Article
- Template-assisted synthesis of adenine-mutagenized cDNA by a retroelement protein complex.Nucleic acids research · 2018Article
- Deep sequencing of HIV-1 reverse transcripts reveals the multifaceted antiviral functions of APOBEC3G.Nature microbiology · 2018Article
- Article
- HIV-1 and HIV-2 exhibit divergent interactions with HLTF and UNG2 DNA repair proteins.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Pre-steady state kinetic analysis of HIV-1 reverse transcriptase for non-canonical ribonucleoside triphosphate incorporation and DNA synthesis from ribonucleoside-containing DNA template.Antiviral research · 2015Article
- GTP activator and dNTP substrates of HIV-1 restriction factor SAMHD1 generate a long-lived activated state.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Vpx rescue of HIV-1 from the antiviral state in mature dendritic cells is independent of the intracellular deoxynucleotide concentration.Retrovirology · 2014Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Terminally differentiated/non-dividing macrophages contain extremely low cellular dNTP concentrations (20-40 nm), compared with activated CD4(+) T cells (2-5 μm). However, our LC-MS/MS study revealed that the non-canonical dUTP concentration (2.9 μm) is ∼60 times higher than TTP in macrophages, whereas the concentrations of dUTP and TTP in dividing human primary lymphocytes are very similar. Specifically, we evaluated the contribution of HIV-1 reverse transcriptase to proviral DNA uracilation under the physiological conditions found in HIV-1 target cells. Indeed, biochemical simulation of HIV-1 reverse transcription demonstrates that HIV-1 RT efficiently incorporates dUTP in the macrophage nucleotide pools but not in the T cell nucleotide pools. Measurement of both pre-steady state and steady state kinetic parameters of dUTP incorporation reveals minimal selectivity of HIV-1 RT for TTP over dUTP, implying that the cellular dUTP/TTP ratio determines the frequency of HIV-1 RT-mediated dUTP incorporation. The RT of another lentivirus, simian immunodeficiency virus, also displays efficient dUTP incorporation in the dNTP/dUTP pools found in macrophages but not in T cells. Finally, 2',3'-dideoxyuridine was inhibitory to HIV-1 proviral DNA synthesis in macrophages but not in T cells. The data presented demonstrates that the non-canonical dUTP was abundant relative to TTP, and efficiently incorporated during HIV-1 reverse transcription, particularly in non-dividing macrophages.
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