ArticleProceedings of the National Academy of Sciences of the United States of America2017
Vpx overcomes a SAMHD1-independent block to HIV reverse transcription that is specific to resting CD4 T cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
- 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
- Chimeric antigen receptor dendritic cells suppress melanoma growth in preclinical cancer models.Journal for immunotherapy of cancer · 2025Article
- Blockade ofmBio · 2025Article
- Transcriptomic Analysis Reveals Key Pathways Influenced by HIV-2 Vpx.International journal of molecular sciences · 2025Article
- Keratin-72 restricts HIV-1 infection in resting CD4Nature communications · 2025Article
- CRL4-DCAF1 Ubiquitin Ligase Dependent Functions of HIV Viral Protein R and Viral Protein X.Viruses · 2024Review
- Novel Vpx virus-like particles to improve cytarabine treatment response against acute myeloid leukemia.Clinical and experimental medicine · 2024Article
- Review
- Checkpoint inhibitor-expressing lentiviral vaccine suppresses tumor growth in preclinical cancer models.Journal for immunotherapy of cancer · 2024Article
- New Insights into HIV Life Cycle, Th1/Th2 Shift during HIV Infection and Preferential Virus Infection of Th2 Cells: Implications of Early HIV Treatment Initiation and Care.Life (Basel, Switzerland) · 2024Review
- Article
- Tissue-like environments shape functional interactions of HIV-1 with immature dendritic cells.EMBO reports · 2023Article
- Antiretroviral Treatment of HIV-2 Infection: Available Drugs, Resistance Pathways, and Promising New Compounds.International journal of molecular sciences · 2023Review
- HUSH-mediated HIV silencing is independent of TASOR phosphorylation on threonine 819.Retrovirology · 2022Article
- Article
- HIV-2/SIV Vpx antagonises NF-κB activation by targeting p65.Retrovirology · 2022Article
- SAMHD1 Promotes the Antiretroviral Adaptive Immune Response in Mice Exposed to Lipopolysaccharide.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- The CRL4The EMBO journal · 2021Article
- Binding to DCAF1 distinguishes TASOR and SAMHD1 degradation by HIV-2 Vpx.PLoS pathogens · 2021Article
- Y44A Mutation in the Acidic Domain of HIV-2 Tat Impairs Viral Reverse Transcription and LTR-Transactivation.International journal of molecular sciences · 2020Article
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Authors and funding
20 authors at 11 institutions in 2 countries.
Funding
Abstract
Early after entry into monocytes, macrophages, dendritic cells, and resting CD4 T cells, HIV encounters a block, limiting reverse transcription (RT) of the incoming viral RNA genome. In this context, dNTP triphosphohydrolase SAM domain and HD domain-containing protein 1 (SAMHD1) has been identified as a restriction factor, lowering the concentration of dNTP substrates to limit RT. The accessory lentiviral protein X (Vpx) proteins from the major simian immunodeficiency virus of rhesus macaque, sooty mangabey, and HIV-2 (SIVsmm/SIVmac/HIV-2) lineage packaged into virions target SAMHD1 for proteasomal degradation, increase intracellular dNTP pools, and facilitate HIV cDNA synthesis. We find that virion-packaged Vpx proteins from a second SIV lineage, SIV of red-capped mangabeys or mandrills (SIVrcm/mnd-2), increased HIV infection in resting CD4 T cells, but not in macrophages, and, unexpectedly, acted in the absence of SAMHD1 degradation, dNTP pool elevation, or changes in SAMHD1 phosphorylation. Vpx rcm/mnd-2 virion incorporation resulted in a dramatic increase of HIV-1 RT intermediates and viral cDNA in infected resting CD4 T cells. These analyses also revealed a barrier limiting HIV-1 infection of resting CD4 T cells at the level of nuclear import. Single amino acid changes in the SAMHD1-degrading Vpx mac239 allowed it to enhance early postentry steps in a Vpx rcm/mnd-2-like fashion. Moreover, Vpx enhanced HIV-1 infection of SAMHD1-deficient resting CD4 T cells of a patient with Aicardi-Goutières syndrome. These results indicate that Vpx, in addition to SAMHD1, overcomes a previously unappreciated restriction for lentiviruses at the level of RT that acts independently of dNTP concentrations and is specific to resting CD4 T cells.
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