Evidence map›Paper›PMID 16439540›Full record

ArticleJournal of virology2006

Modulation of cellular protein trafficking by human immunodeficiency virus type 1 Nef: role of the acidic residue in the ExxxLL motif.

Scott H Coleman, Ricardo Madrid, Nanette Van Damme, Richard S Mitchell, Jerome Bouchet, Cecile Servant, Satish Pillai, Serge Benichou, John C Guatelli

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.2field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
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  13. Mechanisms of HIV-1 Nef function and intracellular signaling.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2011
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. HIV-1 Nef: at the crossroads.Retrovirology · 2008
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 2 countries.

Scott H ColemanUniversity of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA. jguatelli@ucsd.edu
Ricardo Madrid
Nanette Van Damme
Richard S Mitchell
Jerome Bouchet
Cecile Servant
Satish Pillai
Serge Benichou
John C Guatelli
VA San Diego Healthcare System · USCentre National de la Recherche Scientifique · FRInserm · FRUniversity of California, San Diego · US

Funding

VirologyP30AI036214 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Maile Ann Young Karris · 1994 to 2026
$78.4M
HOPE Training GrantT32AI007384 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Sara Gianella Weibel, Scott L Letendre · 1990 to 2026
$9.7M
HIV-1 NEF AND VIRAL INFECTIVITYR01AI038201 · NIAID · VETERANS MEDICAL RESEARCH FDN/SAN DIEGO · PI GUATELLI, JOHN C. · 1996 to 2013
$4.1M
HIV 1 NEF and InfectivityR21AI038201 · NIAID · VETERANS MEDICAL RESEARCH FDN/SAN DIEGO · PI GUATELLI, JOHN · 2003 to 2003
$331k
NIAID NIH HHS AI07384NIAID NIH HHS AI36214NIAID NIH HHS AI38201NIAID NIH HHS P30 AI036214NIAID NIH HHS R01 AI038201NIAID NIH HHS R21 AI038201NIAID NIH HHS T32 AI007384
6 · The paper itself

Abstract

The nef gene contributes to the replication of primate lentiviruses by altering the trafficking of cellular proteins involved in adaptive immunity (class I and II major histocompatibility complex [MHC]) and viral transmission (CD4 and DC-SIGN). A conserved acidic leucine-based sequence (E(160)xxxLL) within human immunodeficiency virus type 1 (HIV-1) Nef binds to the cellular adaptor protein (AP) complexes, which mediate protein sorting into endosomal vesicles. The leucine residues in this motif are required for the down-regulation of CD4 and for the up-regulation of DC-SIGN and the invariant chain of MHC class II, but the role of the acidic residue is unclear. Here, substitution of E160 with uncharged residues impaired the ability of Nef to up-regulate the expression of the invariant chain and DC-SIGN at the cell surface, whereas substitution with a basic residue was required for a similar effect on the down-regulation of CD4. All substitutions of E160 relieved the Nef-mediated block to transferrin uptake. E160 was required for the efficient interaction of Nef with AP-1 and AP-3 and for the stabilization of these complexes on endosomal membranes in living cells. Systematic mutation of the ExxxLL sequence together with correlation of binding and functional data leads to the hypotheses that AP-1 and AP-3 are major cofactors for the effect of Nef on the trafficking of transferrin, are less important but contribute to the modulation of the invariant chain and DC-SIGN, and are least critical for the modulation of CD4. The data suggest that the E160 residue plays a differential role in the modulation of leucine-dependent Nef-targets and support a model in which distinct AP complexes are used by Nef to modulate different cellular proteins.

Indexed as

Protein TransportAdaptor Protein Complex 1Adaptor Protein Complex 3Amino Acid MotifsAmino Acid SubstitutionCD4 AntigensCell Adhesion MoleculesCell LineCell MembraneDC-Specific ICAM-3 Grabbing NonintegrinEndosomesGene Products, nefHistocompatibility Antigens Class IHIV-1HumansIntracellular MembranesAdaptor Protein Complex 1Adaptor Protein Complex 3CD4 AntigensCell Adhesion MoleculesDC-Specific ICAM-3 Grabbing NonintegrinGene Products, nefHistocompatibility Antigens Class ILectins, C-Typenef Gene Products, Human Immunodeficiency VirusReceptors, Cell SurfaceTransferrin

Identifiers

PMID16439540
PMCPMC1367136
OpenAlexW2148960594

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.