ArticleJournal of virology2009
5-Azacytidine can induce lethal mutagenesis in human immunodeficiency virus type 1.
Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 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
58 citing papers in PubMed, 94 citations in OpenAlex.
- Mutation of HIV-1 genomes in a clinical population treated with the mutagenic nucleoside KP1461.PloS one · 2011Trial
- Epigenetic Inhibitor 5-Azacytidine Triggers DIM-2/DIM-5-Dependent Mutagenesis in H3K9me3-Enriched Regions ofJournal of fungi (Basel, Switzerland) · 2026Article
- 1'-Cyanocytidine-5'-isobutyryl is a potent SARS-CoV-2 inhibitor in culture and infected Syrian hamsters.Science advances · 2025Article
- Fidelity Characterization of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and NADC30-like Strain.Viruses · 2024Article
- Viral Evolution Shaped by Host Proteostasis Networks.Annual review of virology · 2023Review
- Ribavirin inhibits the replication of infectious bursal disease virus predominantly through depletion of cellular guanosine pool.Frontiers in veterinary science · 2023Article
- Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity.Viruses · 2022Review
- African Americans' Hemodialysis Treatment Adherence Data Assessment and Presentation: A Precision-Based Paradigm Shift to Support Quality Improvement Activities.Kidney medicine · 2022Article
- IRF7 expression correlates with HIV latency reversal upon specific blockade of immune activation.Frontiers in immunology · 2022Article
- Drug repositioning by merging active subnetworks validated in cancer and COVID-19.Scientific reports · 2021Article
- Distinct Antiretroviral Mechanisms Elicited by a Viral Mutagen.Journal of molecular biology · 2021Article
- Antiviral nucleoside analogs.Chemistry of heterocyclic compounds · 2021Article
- Spontaneous Mutations in HIV-1 Gag, Protease, RT p66 in the First Replication Cycle and How They Appear: Insights from an In Vitro Assay on Mutation Rates and Types.International journal of molecular sciences · 2020Article
- The Roles of Host 5-Methylcytosine RNA Methyltransferases during Viral Infections.International journal of molecular sciences · 2020Review
- Selected nucleos(t)ide-based prescribed drugs and their multi-target activity.European journal of pharmacology · 2019Review
- Distinct dual antiviral mechanism that enhances hepatitis B virus mutagenesis and reduces viral DNA synthesis.Antiviral research · 2019Article
- Synergistic lethal mutagenesis of hepatitis C virus.Antimicrobial agents and chemotherapy · 2019Article
- Brca1 Is Upregulated by 5-Aza-CdR and Promotes DNA Repair and Cell Survival, and Inhibits Neurite Outgrowth in Rat Retinal Neurons.International journal of molecular sciences · 2018Article
- Evidence for the Selective Basis of Transition-to-Transversion Substitution Bias in Two RNA Viruses.Molecular biology and evolution · 2017Article
- 5-Azacytidine Enhances the Mutagenesis of HIV-1 by Reduction to 5-Aza-2'-Deoxycytidine.Antimicrobial agents and chemotherapy · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Ribonucleosides inhibit human immunodeficiency virus type 1 (HIV-1) replication by mechanisms that have not been fully elucidated. Here, we report the antiviral mechanism for the ribonucleoside analog 5-azacytidine (5-AZC). We hypothesized that the anti-HIV-1 activity of 5-AZC was due to an increase in the HIV-1 mutation rate following its incorporation into viral RNA during transcription. However, we demonstrate that 5-AZC's primary antiviral activity can be attributed to its effect on the early phase of HIV-1 replication. Furthermore, the antiviral activity was associated with an increase in the frequency of viral mutants, suggesting that 5-AZC's primary target is reverse transcription. Sequencing analysis showed an enrichment in G-to-C transversion mutations and further supports the idea that reverse transcription is an antiviral target of 5-AZC. These results indicate that 5-AZC is incorporated into viral DNA following reduction to 5-aza-2'-deoxycytidine. Incorporation into the viral DNA leads to an increase in mutant frequency that is consistent with lethal mutagenesis during reverse transcription as the primary antiviral mechanism of 5-AZC. Antiviral activity and increased mutation frequency were also associated with the late phase of HIV-1 replication; however, 5-AZC's effect on the late phase was less robust. These results reveal that the primary antiviral mechanism of 5-AZC can be attributed to its ability to increase the HIV-1 mutation frequency through viral-DNA incorporation during reverse transcription. Our observations indicate that 5-AZC can affect two steps in HIV-1 replication (i.e., transcription and reverse transcription) but that its primary antiviral activity is due to incorporation during reverse transcription.
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.