ArticleJournal of virology2008
Human immunodeficiency virus type 1 Nef induces programmed death 1 expression through a p38 mitogen-activated protein kinase-dependent mechanism.
Article in Journal of virology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Expression Profile and Biological Role of Immune Checkpoints in Disease Progression of HIV/SIV Infection.Viruses · 2022Pooled it
- Beyond oncogenesis: the unexplored benefits of viruses in cancer immunity.Nature reviews. Cancer · 2026Review
- Nef as a driver of immunodeficiency and HIV-associated diseases: insights from mouse models.Frontiers in immunology · 2026Review
- Article
- The Hallmarks of Ageing in Human Immunodeficiency Virus Infection and the Impact of Antiretroviral Therapy on Telomeres: A Molecular Perspective.Current issues in molecular biology · 2025Review
- IL-21 and anti-α4β7 dual therapy during ART promotes immunological and microbiome responses in SIV-infected macaques.JCI insight · 2025Article
- Nef defect attenuates HIV viremia and immune dysregulation in the bone marrow-liver-thymus-spleen (BLTS) humanized mouse model.Virology · 2024Article
- PROTAC-mediated degradation of HIV-1 Nef efficiently restores cell-surface CD4 and MHC-I expression and blocks HIV-1 replication.Cell chemical biology · 2024Article
- Inhibition of SFTSV replication in humanized mice by a subcutaneously administered anti-PD1 nanobody.EMBO molecular medicine · 2024Article
- Unequal distribution of genetically-intact HIV-1 proviruses in cells expressing the immune checkpoint markers PD-1 and/or CTLA-4.Frontiers in immunology · 2023Article
- Immune Checkpoint Molecules and Glucose Metabolism in HIV-Induced T Cell Exhaustion.Biomedicines · 2022Review
- Bioinformatic analysis of PD-1 checkpoint blockade response in influenza infection.BMC genomic data · 2022Article
- Immune checkpoint blockade in HIV.EBioMedicine · 2022Review
- Flow-Cytometry Intracellular Detection and Quantification of HIV1 p24 Antigen and Immunocheckpoint Molecules in T Cells among HIV/AIDS Patients.HIV/AIDS (Auckland, N.Z.) · 2022Article
- PD-1 Blockade Restores the Proliferation of Peripheral Blood Lymphocyte and Inhibits Lymphocyte Apoptosis in a BALB/c Mouse Model of CP BVDV Acute Infection.Frontiers in immunology · 2021Article
- Inhibition of p38 MAPK in combination with ART reduces SIV-induced immune activation and provides additional protection from immune system deterioration.PLoS pathogens · 2018Article
- SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue.PLoS pathogens · 2018Article
- Immune Checkpoints as the Immune System Regulators and Potential Biomarkers in HIV-1 Infection.International journal of molecular sciences · 2018Review
- The HIV-1 accessory proteins Nef and Vpu downregulate total and cell surface CD28 in CD4Retrovirology · 2018Article
- Modulation of Tim-3 Expression by Antigen-Dependent and -Independent Factors on T Cells from Patients with Chronic Hepatitis B Virus Infection.Frontiers in cellular and infection microbiology · 2017Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic viral infection is characterized by the functional impairment of virus-specific T-cell responses. Recent evidence has suggested that the inhibitory receptor programmed death 1 (PD-1) is specifically upregulated on antigen-specific T cells during various chronic viral infections. Indeed, it has been reported that human immunodeficiency virus (HIV)-specific T cells express elevated levels of PD-1 and that this expression correlates with the viral load and inversely with CD4(+) T-cell counts. More importantly, antibody blockade of the PD-1/PD-L1 pathway was sufficient to both increase and stimulate virus-specific T-cell proliferation and cytokine production. However, the mechanisms that mediate HIV-induced PD-1 upregulation are not known. Here, we provide evidence that the HIV type 1 (HIV-1) accessory protein Nef can transcriptionally induce the expression of PD-1 during infection in vitro. Nef-induced PD-1 upregulation requires its proline-rich motif and the activation of the downstream kinase p38. Further, inhibition of Nef activity by p38 MAPK inhibitor effectively blocked PD-1 upregulation, suggesting that p38 MAPK activation is an important initiating event in Nef-mediated PD-1 expression in HIV-1-infected cells. These data demonstrate an important signaling event of Nef in HIV-1 pathogenesis.
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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.