ArticleThe EMBO journal2018
DNA damage induced by topoisomerase inhibitors activates SAMHD1 and blocks HIV-1 infection of macrophages.
Article in The EMBO journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 56 citations in OpenAlex.
- Manipulation of the nucleotide pool in human, bacterial and plant immunity.Nature reviews. Immunology · 2026Review
- Learning from nature: HIV elite controllers as blueprints for a functional cure.Virology journal · 2025Review
- Selective depletion of tumor-associated SAMHD1 enhances chemotherapeutic efficacy and antitumor immune responses.Signal transduction and targeted therapy · 2025Article
- Genotoxic consequences of viral infections.Npj viruses · 2025Review
- SAMHD1 shapes deoxynucleotide triphosphate homeostasis by interconnecting the depletion and biosynthesis of different dNTPs.Nature communications · 2025Article
- CD4 T cell contact drives macrophage cell cycle G0-G1 transition.Signal transduction and targeted therapy · 2024Article
- A Novel Engineering Cell Therapy Platform Mimicking the Immune Thrombocytopenia-Derived Platelets to Inhibit Cytokine Storm in Hemophagocytic Lymphohistiocytosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- Topoisomerase Inhibitors Increase Episomal DNA Expression by Inducing the Integration of Episomal DNA in Hepatic Cells.Pharmaceutics · 2023Article
- Attenuation of reverse transcriptase facilitates SAMHD1 restriction of HIV-1 in cycling cells.Retrovirology · 2023Article
- Targeting SAMHD1: To overcome multiple anti-cancer drugs resistance in hematological malignancies.Genes & diseases · 2023Review
- Systematic comparison of differential expression networks in MTB mono-, HIV mono- and MTB/HIV co-infections for drug repurposing.PLoS computational biology · 2022Article
- Viral Modulation of the DNA Damage Response and Innate Immunity: Two Sides of the Same Coin.Journal of molecular biology · 2022Review
- Genotoxic stress signalling as a driver of macrophage diversity.Cell stress · 2022Review
- Dasatinib: effects on the macrophage phospho proteome with a focus on SAMHD1 and HIV-1 infection.Clinical research in HIV/AIDS · 2022Article
- Nucleic acid binding by SAMHD1 contributes to the antiretroviral activity and is enhanced by the GpsN modification.Nature communications · 2021Article
- New strategies to treat AML: novel insights into AML survival pathways and combination therapies.Leukemia · 2021Review
- Targeting Epigenetics to Cure HIV-1: Lessons From (and for) Cancer Treatment.Frontiers in cellular and infection microbiology · 2021Review
- Mechanisms underlying of antiretroviral drugs in different cellular reservoirs with a focus on macrophages.Virulence · 2020Review
- Orchestrated efforts on host network hijacking: Processes governing virus replication.Virulence · 2020Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
We report that DNA damage induced by topoisomerase inhibitors, including etoposide (ETO), results in a potent block to HIV-1 infection in human monocyte-derived macrophages (MDM). SAMHD1 suppresses viral reverse transcription (RT) through depletion of cellular dNTPs but is naturally switched off by phosphorylation in a subpopulation of MDM found in a G1-like state. We report that SAMHD1 was activated by dephosphorylation following ETO treatment, along with loss of expression of MCM2 and CDK1, and reduction in dNTP levels. Suppression of infection occurred after completion of viral DNA synthesis, at the step of 2LTR circle and provirus formation. The ETO-induced block was completely rescued by depletion of SAMHD1 in MDM Concordantly, infection by HIV-2 and SIVsm encoding the SAMHD1 antagonist Vpx was insensitive to ETO treatment. The mechanism of DNA damage-induced blockade of HIV-1 infection involved activation of p53, p21, decrease in CDK1 expression, and SAMHD1 dephosphorylation. Therefore, topoisomerase inhibitors regulate SAMHD1 and HIV permissivity at a post-RT step, revealing a mechanism by which the HIV-1 reservoir may be limited by chemotherapeutic drugs.
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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.