ArticleNature2011
Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein.
Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 831 papers, 1 of them a synthesis that pooled it.
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Who cites it
831 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,200 citations in OpenAlex.
- Disrupting Mechanisms that Regulate Genomic Repeat Elements to Combat Cancer and Drug Resistance.Frontiers in cell and developmental biology · 2022Pooled it
- Human Immunodeficiency Virus Type 2 Vpx-mediated Degradation of TASOR Activates Innate Immune Sensing of Nucleic Acids in Infected Cells.Journal of molecular biology · 2026Article
- Next-generation macrophage engineering in cancer therapy: From TAM reprogramming to CAR-macrophages.Molecular therapy. Nucleic acids · 2026Review
- Review
- Octameric dGTPase assemblies mediate broad anti-phage defense.Nature communications · 2026Article
- Article
- SUMOylation and ubiquitination reciprocally regulate SMCHD1 antiviral activity against herpes simplex virus 1.PLoS pathogens · 2026Article
- Fingolimod increases cellular resistance to HIV-1 infection and limits viral reservoir size in peripheral CD4+ T-cells.PLoS pathogens · 2026Article
- Transcription start site heterogeneity controls MDA5 sensing of unspliced HIV-1 RNAs.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- ZFP36L2 is an interferon β -induced inhibitor that restricts the nuclear export of HIV-1 transcripts.Nature communications · 2026Article
- Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity.The Journal of biological chemistry · 2026Article
- SAMHD1 depletion restricts SARS-CoV-2 infection by suppressing HNF1-dependent ACE2 expression in lung epithelial cells.PLoS pathogens · 2026Article
- Host restriction factor SAMHD1 does not restrict seasonal influenza virus replication in human epithelial or macrophage-like cells.Virology journal · 2026Article
- Beyond αβ T cells: unlocking the potential of diverse immune cells in CAR modification.Clinical science (London, England : 1979) · 2026Review
- Innate immune cells in chimeric antigen receptor therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Cross-omics mapping of the human HIV restrictome across clinical states, immune-cell compartments, and protein responses.PloS one · 2026Article
- HIV-2 infection as a comparative lens for functional HIV-1 remission.Frontiers in immunology · 2026Review
- Manipulation of the nucleotide pool in human, bacterial and plant immunity.Nature reviews. Immunology · 2026Review
- A homozygous splice-site variant in SAMHD1 shows variable expressivity of Aicardi-Goutières syndrome type 5: a case report and literature review.Frontiers in pediatrics · 2026Article
- Chimeric antigen receptor dendritic cells suppress melanoma growth in preclinical cancer models.Journal for immunotherapy of cancer · 2025Article
771 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Macrophages and dendritic cells have key roles in viral infections, providing virus reservoirs that frequently resist antiviral therapies and linking innate virus detection to antiviral adaptive immune responses. Human immunodeficiency virus 1 (HIV-1) fails to transduce dendritic cells and has a reduced ability to transduce macrophages, due to an as yet uncharacterized mechanism that inhibits infection by interfering with efficient synthesis of viral complementary DNA. In contrast, HIV-2 and related simian immunodeficiency viruses (SIVsm/mac) transduce myeloid cells efficiently owing to their virion-associated Vpx accessory proteins, which counteract the restrictive mechanism. Here we show that the inhibition of HIV-1 infection in macrophages involves the cellular SAM domain HD domain-containing protein 1 (SAMHD1). Vpx relieves the inhibition of lentivirus infection in macrophages by loading SAMHD1 onto the CRL4(DCAF1) E3 ubiquitin ligase, leading to highly efficient proteasome-dependent degradation of the protein. Mutations in SAMHD1 cause Aicardi-Goutières syndrome, a disease that produces a phenotype that mimics the effects of a congenital viral infection. Failure to dispose of endogenous nucleic acid debris in Aicardi-Goutières syndrome results in inappropriate triggering of innate immune responses via cytosolic nucleic acids sensors. Thus, our findings show that macrophages are defended from HIV-1 infection by a mechanism that prevents an unwanted interferon response triggered by self nucleic acids, and uncover an intricate relationship between innate immune mechanisms that control response to self and to retroviral pathogens.
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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.