ArticleMolecular biology of the cell2006
The Nef protein of human immunodeficiency virus is a broad-spectrum modulator of chemokine receptor cell surface levels that acts independently of classical motifs for receptor endocytosis and Galphai signaling.
Article in Molecular biology of the cell, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- HIV-1 manipulates CD96 on CD4Science advances · 2025Article
- No detectable differences in Nef-mediated downregulation of HLA-I and CD4 molecules among HIV-1 group M lineages circulating in Cameroon, where the pandemic originated.Frontiers in virology (Lausanne, Switzerland) · 2024Article
- Phylogenetic Reconstruction and Functional Characterization of the Ancestral Nef Protein of Primate Lentiviruses.Molecular biology and evolution · 2023Article
- Neutron Reflectometry and Molecular Simulations Demonstrate HIV-1 Nef Homodimer Formation on Model Lipid Bilayers.Journal of molecular biology · 2023Article
- Article
- How HIV Nef Proteins Hijack Membrane Traffic To Promote Infection.Journal of virology · 2019Review
- HIV-1 Balances the Fitness Costs and Benefits of Disrupting the Host Cell Actin Cytoskeleton Early after Mucosal Transmission.Cell host & microbe · 2019Article
- HIV-1 Nef and Vpu are functionally redundant broad-spectrum modulators of cell surface receptors, including tetraspanins.Journal of virology · 2014Article
- Host factors determine differential disease progression after infection with nef-deleted simian immunodeficiency virus.The Journal of general virology · 2014Article
- HIV-1 Nef down-modulates C-C and C-X-C chemokine receptors via ubiquitin and ubiquitin-independent mechanism.PloS one · 2014Article
- HIV-1 Nef impairs heterotrimeric G-protein signaling by targeting Gα(i2) for degradation through ubiquitination.The Journal of biological chemistry · 2012Article
- Identification of a highly conserved valine-glycine-phenylalanine amino acid triplet required for HIV-1 Nef function.Retrovirology · 2012Article
- One protein to rule them all: modulation of cell surface receptors and molecules by HIV Nef.Current HIV research · 2011Review
- SDF-1/CXCL12 production by mature dendritic cells inhibits the propagation of X4-tropic HIV-1 isolates at the dendritic cell-T-cell infectious synapse.Journal of virology · 2010Article
- Lentiviral Nef proteins utilize PAK2-mediated deregulation of cofilin as a general strategy to interfere with actin remodeling.Journal of virology · 2010Article
- Molecular Mechanisms of Neurodegenerative Diseases Induced by Human Retroviruses: A Review.American journal of infectious diseases · 2009Article
- Human immunodeficiency virus type 1 Nef incorporation into virions does not increase infectivity.Journal of virology · 2009Article
- Human immunodeficiency virus type 1 envelope gp120 induces a stop signal and virological synapse formation in noninfected CD4+ T cells.Journal of virology · 2008Article
- Design and in vitro characterization of highly sst2-selective somatostatin antagonists suitable for radiotargeting.Journal of medicinal chemistry · 2008Article
- Viral modulation of T-cell receptor signaling.Journal of virology · 2008Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemokine receptors (CKRs) are important physiological mediators of immune defense, inflammatory responses, and angiogenesis, and they have also been implicated in a number of viral disease processes. Here, we report that the Nef protein of human immunodeficiency virus (HIV) reduces cell surface levels of eight different members of the CC- and CXC-family of CKRs by up to 92%. This broad-range activity required specific elements in HIV(SF2) Nef, including the proline-rich motif P73P76P79P82 as well as the acidic cluster motif E66E67E68E69, and Nef expression induced a marked perinuclear accumulation of CKRs. Surprisingly, receptor mutagenesis demonstrated that the cytoplasmic tail of CCR5 and CXCR4, which is critical for basal and ligand-mediated endocytosis, was completely dispensable for this Nef activity. In contrast, triple-mutation of the highly conserved DRY motif in the second intracellular CKR loop abolished the Nef-mediated down-regulation of CXCR4 independently of this motif's role in CKR binding to heterotrimeric G proteins and signaling via the Galphai subunit. Thus, we identify the lentiviral pathogenicity factor Nef as a unique and broad-range modulator of CKR cell surface levels. Nef uses a mechanism that is distinct from well-established pathways orchestrating CKR metabolism and offers an interesting tool to study the multifaceted biology of CKRs.
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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.