ArticleProceedings of the National Academy of Sciences of the United States of America2011
HIV DNA is heavily uracilated, which protects it from autointegration.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- HIV Genome-Wide Protein Associations: a Review of 30 Years of Research.Microbiology and molecular biology reviews : MMBR · 2016Pooled it
- Review
- CRL4-DCAF1 Ubiquitin Ligase Dependent Functions of HIV Viral Protein R and Viral Protein X.Viruses · 2024Review
- Repair of APOBEC3G-Mutated Retroviral DNAJournal of virology · 2021Article
- 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
- Deoxyuracil in DNA and disease: Genomic signal or managed situation?DNA repair · 2019Review
- Graphene oxide-based biosensing platform for rapid and sensitive detection of HIV-1 protease.Analytical and bioanalytical chemistry · 2018Article
- Deep sequencing of HIV-1 reverse transcripts reveals the multifaceted antiviral functions of APOBEC3G.Nature microbiology · 2018Article
- Unique Features and Anti-microbial Targeting of Folate- and Flavin-Dependent Methyltransferases Required for Accurate Maintenance of Genetic Information.Frontiers in microbiology · 2018Review
- Specific reverse transcriptase slippage at the HIV ribosomal frameshift sequence: potential implications for modulation of GagPol synthesis.Nucleic acids research · 2017Article
- The DDB1-DCAF1-Vpr-UNG2 crystal structure reveals how HIV-1 Vpr steers human UNG2 toward destruction.Nature structural & molecular biology · 2016Article
- 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
- Detection of uracil within DNA using a sensitive labeling method for in vitro and cellular applications.Nucleic acids research · 2016Article
- APOBEC3G-Mediated G-to-A Hypermutation of the HIV-1 Genome: The Missing Link in Antiviral Molecular Mechanisms.Frontiers in microbiology · 2016Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Human immune cells infected by HIV naturally contain high uracil content, and HIV reverse transcriptase (RT) does not distinguish between dUTP and dTTP. Many DNA viruses and retroviruses encode a dUTPase or uracil-DNA glycosylase (UNG) to counteract uracil incorporation. However, although HIV virions are thought to contain cellular UNG2, replication of HIV produced in cells lacking UNG activity does not appear to be impaired. Here we show that HIV reverse transcripts generated in primary human immune cells are heavily uracilated (>500 uracils per 10 kb HIV genome). We find that HIV DNA uracilation, rather than being dangerous, may promote the early phase of the viral life cycle. Shortly after reverse transcription, the ends of the HIV DNA are activated by the viral integrase (IN) in preparation for chromosomal insertion. However, the activated ends can attack the viral DNA itself in a suicidal side pathway, called autointegration. We find here that uracilation of target DNA inhibits the strand transfer of HIV DNA ends by IN, thereby inhibiting autointegration and facilitating chromosomal integration and viral replication. When uracilation is increased by incubating uracil-poor cells in the presence of increasing concentrations of dUTP or by infecting with virus that contains the cytosine deaminase APOBEC3G (A3G), the proportion of reverse transcripts that undergo suicidal autointegration decreases. Thus, HIV tolerates, or even benefits from, nonmutagenic uracil incorporation during reverse transcription in human immune cells.
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