ArticleThe Journal of experimental medicine1999
Induction of Fas ligand expression by HIV involves the interaction of Nef with the T cell receptor zeta chain.
Article in The Journal of experimental medicine, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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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.
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Who cites it
70 citing papers in PubMed, 241 citations in OpenAlex.
- Antigen specificities of HIV-infected cells: A role in infection and persistence?Journal of virus eradication · 2023Review
- Article
- Implications of HIV-1 Nef for "Shock and Kill" Strategies to Eliminate Latent Viral Reservoirs.Viruses · 2018Review
- Intrinsic properties and plasma membrane trafficking route of Src family kinase SH4 domains sensitive to retargeting by HIV-1 Nef.The Journal of biological chemistry · 2018Article
- Primate Lentiviruses Modulate NF-κB Activity by Multiple Mechanisms to Fine-Tune Viral and Cellular Gene Expression.Frontiers in microbiology · 2017Review
- Lipopeptides: a novel antigen repertoire presented by major histocompatibility complex class I molecules.Immunology · 2016Review
- Review
- Heterologous Src homology 4 domains support membrane anchoring and biological activity of HIV-1 Nef.The Journal of biological chemistry · 2014Article
- The activity of Nef on HIV-1 infectivity.Frontiers in microbiology · 2014Review
- The enduring tale of T cells in HIV immunopathogenesis.The Indian journal of medical research · 2013Review
- T-Cell Signaling in HIV-1 Infection.The open virology journal · 2013Article
- Modulation of HIV pathogenesis and T-cell signaling by HIV-1 Nef.Future virology · 2012Article
- CD4+ T cell depletion in human immunodeficiency virus (HIV) infection: role of apoptosis.Viruses · 2011Review
- Pro- and anti-apoptotic CD95 signaling in T cells.Cell communication and signaling : CCS · 2011Article
- Mechanisms of HIV envelope-induced T lymphocyte apoptosis.Virologica Sinica · 2010Review
- Alkylating HIV-1 Nef - a potential way of HIV intervention.AIDS research and therapy · 2010Article
- Article
- Inhibition of human immunodeficiency virus type 1 by triciribine involves the accessory protein nef.Antimicrobial agents and chemotherapy · 2010Article
- A flow cytometry-based FRET assay to identify and analyse protein-protein interactions in living cells.PloS one · 2010Article
- Pseudo-merohedral twinning and noncrystallographic symmetry in orthorhombic crystals of SIVmac239 Nef core domain bound to different-length TCRzeta fragments.Acta crystallographica. Section D, Biological crystallography · 2010Article
10 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
9 authors at 3 institutions in 2 countries.
Funding
Abstract
During HIV/SIV infection, there is widespread programmed cell death in infected and, perhaps more importantly, uninfected cells. Much of this apoptosis is mediated by Fas-Fas ligand (FasL) interactions. Previously we demonstrated in macaques that induction of FasL expression and apoptotic cell death of both CD4(+) and CD8(+) T cells by SIV is dependent on a functional nef gene. However, the molecular mechanism whereby HIV-1 induces the expression of FasL remained poorly understood. Here we report a direct association of HIV-1 Nef with the zeta chain of the T cell receptor (TCR) complex and the requirement of both proteins for HIV-mediated upregulation of FasL. Expression of FasL through Nef depended upon the integrity of the immunoreceptor tyrosine-based activation motifs (ITAMs) of the TCR zeta chain. Conformation for the importance of zeta for Nef-mediated signaling in T cells came from an independent finding. A single ITAM motif of zeta but not CD3epsilon was both required and sufficient to promote activation and binding of the Nef-associated kinase (NAK/p62). Our data imply that Nef can form a signaling complex with the TCR, which bypasses the requirement of antigen to initiate T cell activation and subsequently upregulation of FasL expression. Thus, our study may provide critical insights into the molecular mechanism whereby the HIV-1 accessory protein Nef contributes to the pathogenesis of HIV.
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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.