ArticleProceedings of the National Academy of Sciences of the United States of America2000
The Nef protein of HIV-1 associates with rafts and primes T cells for activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00721305 (Antiretroviral Effect of Lovastatin on HIV-1-infected Individuals Without Highly Active Antiretroviral Therapy), which is not on this map. Cited by 108 papers.
What it found
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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.
Antiretroviral Effect of Lovastatin on HIV-1-infected Individuals Without Highly Active Antiretroviral Therapy (HAART): A Phase-II Randomized Clinical Trial (RCT)
Who cites it
108 citing papers in PubMed, 270 citations in OpenAlex.
- Trial
- HIV Nef disrupts Lck signaling by inducing aberrant phosphorylation of its substrates.ImmunoHorizons · 2025Article
- HIV protein Nef expression in human microglia drives the release of distinct Nef-containing extracellular vesicles.Extracellular vesicles and circulating nucleic acids · 2025Article
- Review
- Kinetic investigation reveals an HIV-1 Nef-dependent increase in AP-2 recruitment and productivity at endocytic sites.Molecular biology of the cell · 2024Article
- Novel role of HIV-1 Nef in regulating the ubiquitination of cellular proteins.Frontiers in cellular and infection microbiology · 2023Article
- Lentiviral Nef Proteins Differentially Govern the Establishment of Viral Latency.Journal of virology · 2022Article
- HIV-1-Mediated Acceleration of Oncovirus-Related Non-AIDS-Defining Cancers.Biomedicines · 2022Review
- A Critical Review of the Biochemical Mechanisms and Epigenetic Modifications in HIV- and Antiretroviral-Induced Metabolic Syndrome.International journal of molecular sciences · 2021Review
- Elastic deformations mediate interaction of the raft boundary with membrane inclusions leading to their effective lateral sorting.Scientific reports · 2020Article
- Role of the Ubiquitin Proteasome System (UPS) in the HIV-1 Life Cycle.International journal of molecular sciences · 2019Review
- Article
- Identification of SERINC5-001 as the Predominant Spliced Isoform for HIV-1 Restriction.Journal of virology · 2017Article
- Article
- Tuning of AKT-pathway by Nef and its blockade by protease inhibitors results in limited recovery in latently HIV infected T-cell line.Scientific reports · 2016Article
- Molecular characterization of HIV-1 Nef and ACOT8 interaction: insights from in silico structural predictions and in vitro functional assays.Scientific reports · 2016Article
- Proteomic profiling of SupT1 cells reveal modulation of host proteins by HIV-1 Nef variants.PloS one · 2015Article
- Viremic long-term nonprogressive HIV-1 infection is not associated with abnormalities in known Nef functions.Retrovirology · 2014Article
- The activity of Nef on HIV-1 infectivity.Frontiers in microbiology · 2014Review
- Suppression of Foxo1 activity and down-modulation of CD62L (L-selectin) in HIV-1 infected resting CD4 T cells.PloS one · 2014Article
48 more citing papers are in PubMed but not listed here.
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
The Nef protein is an important virulence factor of primate lentiviruses, yet the mechanisms by which it exerts this influence are imperfectly understood. Here, using an inducible system, we demonstrate that Nef increases IL-2 secretion from T cells stimulated via CD3 or CD28. This effect requires the conservation of the Nef myristoylation signal and SH3-binding proline-based motif. Together with several proteins involved in the initiation and propagation of T cell signaling, Nef associates with membrane microdomains known as rafts. The Nef-mediated superinduction of IL-2 reflects the activation of both NFAT and NFkappaB. Accordingly, Nef also enhances HIV-1 transcription in response to CD3 or CD28 stimulation. Nef-induced IL-2 hyperresponsiveness is also observed in primary CD4 lymphocytes. Overall, these data suggest that Nef acts at the level of rafts to prime T cells for activation. Likely consequences of this effect are the promotion of HIV-1 replication and the facilitation of virus spread.
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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.