ArticleProceedings of the National Academy of Sciences of the United States of America2013
Uracil DNA glycosylase initiates degradation of HIV-1 cDNA containing misincorporated dUTP and prevents viral integration.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 73 citations in OpenAlex.
- Antiviral defence is a conserved function of diverse bacterial DNA glycosylases.Nature microbiology · 2026Article
- Uridine Embedded within DNA is Repaired by Uracil DNA Glycosylase via a Mechanism Distinct from That of Ribonuclease H2.Journal of the American Chemical Society · 2025Article
- HIV-1 Vpr Functions in Primary CD4Viruses · 2024Review
- Human DNA tumor viruses evade uracil-mediated antiviral immunity.PLoS pathogens · 2023Article
- Replication-competent HIV-1 in human alveolar macrophages and monocytes despite nucleotide pools with elevated dUTP.Retrovirology · 2022Article
- Structure of HIV-1 Vpr in complex with the human nucleotide excision repair protein hHR23A.Nature communications · 2021Article
- Repair of APOBEC3G-Mutated Retroviral DNAJournal of virology · 2021Article
- Mitochondrial CMPK2 mediates immunomodulatory and antiviral activities through IFN-dependent and IFN-independent pathways.iScience · 2021Article
- Inhibition of Human Uracil DNA Glycosylase Sensitizes a Large Fraction of Colorectal Cancer Cells to 5-Fluorodeoxyuridine and Raltitrexed but Not Fluorouracil.Molecular pharmacology · 2021Article
- Review
- The dUTPase of caprine arthritis-encephalitis virus negatively regulates interferon signaling pathway.Iranian journal of veterinary research · 2021Article
- Review
- Deoxyuracil in DNA in health and disease.Current opinion in clinical nutrition and metabolic care · 2020Review
- The Essential Co-Option of Uracil-DNA Glycosylases by Herpesviruses Invites Novel Antiviral Design.Microorganisms · 2020Review
- Deficient uracil base excision repair leads to persistent dUMP in HIV proviruses during infection of monocytes and macrophages.PloS one · 2020Article
- 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
- Article
- 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
- CMPK2 and BCL-G are associated with type 1 interferon-induced HIV restriction in humans.Science advances · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
HIV-1 reverse transcriptase discriminates poorly between dUTP and dTTP, and accordingly, viral DNA products become heavily uracilated when viruses infect host cells that contain high ratios of dUTP:dTTP. Uracilation of invading retroviral DNA is thought to be an innate immunity barrier to retroviral infection, but the mechanistic features of this immune pathway and the cellular fate of uracilated retroviral DNA products is not known. Here we developed a model system in which the cellular dUTP:dTTP ratio can be pharmacologically increased to favor dUTP incorporation, allowing dissection of this innate immunity pathway. When the virus-infected cells contained elevated dUTP levels, reverse transcription was found to proceed unperturbed, but integration and viral protein expression were largely blocked. Furthermore, successfully integrated proviruses lacked detectable uracil, suggesting that only nonuracilated viral DNA products were integration competent. Integration of the uracilated proviruses was restored using an isogenic cell line that had no detectable human uracil DNA glycosylase (hUNG2) activity, establishing that hUNG2 is a host restriction factor in cells that contain high dUTP. Biochemical studies in primary cells established that this immune pathway is not operative in CD4+ T cells, because these cells have high dUTPase activity (low dUTP), and only modest levels of hUNG activity. Although monocyte-derived macrophages have high dUTP levels, these cells have low hUNG activity, which may diminish the effectiveness of this restriction pathway. These findings establish the essential elements of this pathway and reconcile diverse observations in the literature.
Indexed as
Identifiers
What OpenQuestion holds
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.