ArticleThe EMBO journal2001
Mechanism for down-regulation of CD28 by Nef.
Article in The EMBO journal, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 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
107 citing papers in PubMed, 204 citations in OpenAlex.
- AP2: an indispensable host factor in virus infection.Journal of virology · 2026Review
- Nef as a driver of immunodeficiency and HIV-associated diseases: insights from mouse models.Frontiers in immunology · 2026Review
- Ancestral reconstruction supports that loss of Nef-mediated T cell modulation coincided with the emergence of pathogenic lentiviruses.Journal of virology · 2025Article
- HIV-1 Nef activates proviral DNA transcription by recruiting Src kinase to phosphorylate host protein Nef-associated factor 1 to compromise its viral restrictive function.Journal of virology · 2025Article
- Non-AUG HIV-1 uORF translation elicits specific T cell immune response and regulates viral transcript expression.Nature communications · 2025Article
- E3 Ubiquitin Ligases in Gammaherpesviruses and HIV: A Review of Virus Adaptation and Exploitation.Viruses · 2023Review
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- Article
- Residues TRetrovirology · 2021Article
- Viral Interactions with Adaptor-Protein Complexes: A Ubiquitous Trait among Viral Species.International journal of molecular sciences · 2021Review
- Characterization of HIV-induced remodeling reveals differences in infection susceptibility of memory CD4Cell reports · 2021Article
- Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction.Viruses · 2021Article
- HIV-1 Nef counteracts autophagy restriction by enhancing the association between BECN1 and its inhibitor BCL2 in a PRKN-dependent manner.Autophagy · 2021Article
- HIV efficiently infects T cells from the endometrium and remodels them to promote systemic viral spread.eLife · 2020Article
- A Novel HIV-1 Nef Mutation in a Primary Pediatric Isolate Impairs MHC-Class I Downregulation and Cytopathicity.AIDS research and human retroviruses · 2020Article
- Structure of HIV-2 Nef Reveals Features Distinct from HIV-1 Involved in Immune Regulation.iScience · 2020Article
- Ubiquitination and SUMOylation in HIV Infection: Friends and Foes.Current issues in molecular biology · 2020Review
- Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant.PloS one · 2020Article
- How HIV Nef Proteins Hijack Membrane Traffic To Promote Infection.Journal of virology · 2019Review
- Implications of HIV-1 Nef for "Shock and Kill" Strategies to Eliminate Latent Viral Reservoirs.Viruses · 2018Review
47 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
3 authors at 1 institution in 1 country.
Funding
Abstract
SIV and HIV Nef proteins disrupt T-cell receptor machinery by down-modulating cell surface expression of CD4 and expression or signaling of CD3-TCR. Nef also down-modulates class I major histocompatibility complex (MHC) surface expression. We show that SIV and HIV-1 Nefs down-modulate CD28, a major co-stimulatory receptor that mediates effective T-cell activation, by accelerating CD28 endocytosis. The effects of Nef on CD28, CD4, CD3 and class I MHC expression are all genetically separable, indicating that all are selected independently. In cells expressing a Nef-green fluorescent protein (GFP) fusion, CD28 co-localizes with the AP-2 clathrin adaptor and Nef-GFP. Mutations that disrupt Nef interaction with AP-2 disrupt CD28 down-regulation. Furthermore, HIV and SIV Nefs use overlapping but distinct target sites in the membrane-proximal region of the CD28 cytoplasmic domain. Thus, Nef probably induces CD28 endocytosis via the AP-2 pathway, and this involves a ternary complex containing Nef, AP-2 and CD28. The likely consequence of the concerted down-regulation of CD28, CD4 and/or CD3 by Nef is disruption of antigen-specific signaling machineries in infected T cells following a productive antigen recognition event.
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What OpenQuestion holds
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.