ArticleCell host & microbe2012
The ability of primate lentiviruses to degrade the monocyte restriction factor SAMHD1 preceded the birth of the viral accessory protein Vpx.
Article in Cell host & microbe, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 164 papers.
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164 citing papers in PubMed, 264 citations in OpenAlex.
- Self-Dimerization Induced Proximity Targeting Chimeras (SDIPTAC) Lead to DCAF1 Loss of Function and Inhibition of HIV Replication.Journal of medicinal chemistry · 2026Article
- HIV Vpr activates a nucleolar-specific ATR pathway to degrade the nucleolar stress sensor CCDC137.Nucleic acids research · 2025Article
- Deciphering lentiviral Vpr/Vpx determinants required for HUSH and SAMHD1 antagonism highlights the molecular plasticity of these evolutionary conflicts.Journal of virology · 2025Article
- Keratin-72 restricts HIV-1 infection in resting CD4Nature communications · 2025Article
- Deubiquitinase USP37 enhances the anti-HIV-2/SIV ability of the host restriction factor SAMHD1.Journal of virology · 2025Article
- Genotoxic consequences of viral infections.Npj viruses · 2025Review
- Novel Vpx virus-like particles to improve cytarabine treatment response against acute myeloid leukemia.Clinical and experimental medicine · 2024Article
- SAMHD1 expression contributes to doxorubicin resistance and predicts survival outcomes in diffuse large B-cell lymphoma patients.NAR cancer · 2024Article
- FREEDA: An automated computational pipeline guides experimental testing of protein innovation.The Journal of cell biology · 2023Article
- Attenuation of reverse transcriptase facilitates SAMHD1 restriction of HIV-1 in cycling cells.Retrovirology · 2023Article
- FREEDA: an automated computational pipeline guides experimental testing of protein innovation by detecting positive selection.bioRxiv : the preprint server for biology · 2023Article
- Directly injected lentiviral vector-based T cell vaccine protects mice against acute and chronic viral infection.JCI insight · 2022Article
- Review
- Viral Modulation of the DNA Damage Response and Innate Immunity: Two Sides of the Same Coin.Journal of molecular biology · 2022Review
- SAMHD1 Promotes the Antiretroviral Adaptive Immune Response in Mice Exposed to Lipopolysaccharide.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- HIV-2 Vpx neutralizes host restriction factor SAMHD1 to promote viral pathogenesis.Scientific reports · 2021Article
- Role of Intracellular Distribution of Feline and Bovine SAMHD1 Proteins in Lentiviral Restriction.Virologica Sinica · 2021Article
- Binding to DCAF1 distinguishes TASOR and SAMHD1 degradation by HIV-2 Vpx.PLoS pathogens · 2021Article
- Structural and functional characterization explains loss of dNTPase activity of the cancer-specific R366C/H mutant SAMHD1 proteins.The Journal of biological chemistry · 2021Article
- Structural insights into Cullin4-RING ubiquitin ligase remodelling by Vpr from simian immunodeficiency viruses.PLoS pathogens · 2021Article
104 more citing papers are in PubMed but not listed here.
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6 authors at 2 institutions in 1 country.
Funding
Abstract
The human SAMHD1 protein potently restricts lentiviral infection in dendritic cells and monocyte/macrophages but is antagonized by the primate lentiviral protein Vpx, which targets SAMHD1 for degradation. However, only two of eight primate lentivirus lineages encode Vpx, whereas its paralog, Vpr, is conserved across all extant primate lentiviruses. We find that not only multiple Vpx but also some Vpr proteins are able to degrade SAMHD1, and such antagonism led to dramatic positive selection of SAMHD1 in the primate subfamily Cercopithecinae. Residues that have evolved under positive selection precisely determine sensitivity to Vpx/Vpr degradation and alter binding specificity. By overlaying these functional analyses on a phylogenetic framework of Vpr and Vpx evolution, we can decipher the chronology of acquisition of SAMHD1-degrading abilities in lentiviruses. We conclude that vpr neofunctionalized to degrade SAMHD1 even prior to the birth of a separate vpx gene, thereby initiating an evolutionary arms race with SAMHD1.
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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.