Evidence map›Paper›PMID 12414957›Full record

ArticleJournal of virology2002

Direct binding of human immunodeficiency virus type 1 Nef to the major histocompatibility complex class I (MHC-I) cytoplasmic tail disrupts MHC-I trafficking.

Maya Williams, Jeremiah F Roeth, Matthew R Kasper, Rebekah I Fleis, Chris G Przybycin, Kathleen L Collins

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
3.4field-weighted citation impact, top 6% 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

55 citing papers in PubMed, 114 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Intracellular trafficking of HLA-E and its regulation.The Journal of experimental medicine · 2023
    Article
  5. Article
  6. The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-Ι.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  7. Article
  8. Article
  9. Review
  10. Concanamycin A counteracts HIV-1 Nef to enhance immune clearance of infected primary cells by cytotoxic T lymphocytes.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Improving HIV proteome annotation: new features of BioAfrica HIV Proteomics Resource.Database : the journal of biological databases and curation · 2016
    Article
  18. Article
  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

6 authors at 1 institution in 1 country.

Maya WilliamsGraduate Program in Cellular and Molecular Biology, University of Michigan. University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
Jeremiah F Roeth
Matthew R Kasper
Rebekah I Fleis
Chris G Przybycin
Kathleen L Collins
University of Michigan–Ann Arbor · US

Funding

CELLULAR AND MOLECULAR BIOLOGY AT MICHIGANT32GM007315 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PUTHENVEEDU, MANOJKUMAR A · 1985 to 2021
$12.8M
PREDOCTORAL TRAINING IN GENETICST32GM007544 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MORAN, JOHN V. · 1985 to 2022
$11.3M
Molecular Mechanisms of Microbial Pathogenesis Training ProgramT32AI007528 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CARRUTHERS, VERNON BRUCE · 1998 to 2024
$6.8M
Molecular Mechanisms of HIV's Immune EvasionR01AI046998 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COLLINS, KATHLEEN L. · 2000 to 2013
$4.7M
NIAID NIH HHS 5T32 AI07528NIAID NIH HHS R01 AI046998NIAID NIH HHS R01 AI46998NIAID NIH HHS T32 AI007528NIGMS NIH HHS 5T32 GM07544NIGMS NIH HHS GM07315NIGMS NIH HHS T32 GM007315NIGMS NIH HHS T32 GM007544
6 · The paper itself

Abstract

Nef, an essential pathogenic determinant for human immunodeficiency virus type 1, has multiple functions that include disruption of major histocompatibility complex class I molecules (MHC-I) and CD4 and CD28 cell surface expression. The effects of Nef on MHC-I have been shown to protect infected cells from cytotoxic T-lymphocyte recognition by downmodulation of a subset of MHC-I (HLA-A and -B). The remaining HLA-C and -E molecules prevent recognition by natural killer (NK) cells, which would otherwise lyse cells expressing small amounts of MHC-I. Specific amino acid residues in the MHC-I cytoplasmic tail confer sensitivity to Nef, but their function is unknown. Here we show that purified Nef binds directly to the HLA-A2 cytoplasmic tail in vitro and that Nef forms complexes with MHC-I that can be isolated from human cells. The interaction between Nef and MHC-I appears to be weak, indicating that it may be transient or stabilized by other factors. Supporting the fact that these molecules interact in vivo, we found that Nef colocalizes with HLA-A2 molecules in a perinuclear distribution inside cells. In addition, we demonstrated that Nef fails to bind the HLA-E tail and also fails to bind HLA-A2 tails with deletions of amino acids necessary for MHC-I downmodulation. These data provide an explanation for differential downmodulation of MHC-I allotypes by Nef. In addition, they provide the first direct evidence indicating that Nef functions as an adaptor molecule able to link MHC-I to cellular trafficking proteins.

Indexed as

Amino Acid SequenceAnimalsBase SequenceBinding SitesCell LineCell NucleusDNA, RecombinantDNA, ViralGene Products, nefH-2 AntigensHeLa CellsHistocompatibility Antigens Class IHIV-1HLA-A2 AntigenHLA AntigensHLA-E AntigensDNA, RecombinantDNA, ViralGene Products, nefH-2 AntigensH-2K(K) antigenHistocompatibility Antigens Class IHLA-A2 AntigenHLA AntigensHLA-E Antigensnef Gene Products, Human Immunodeficiency VirusRecombinant Fusion Proteins

Identifiers

PMID12414957
PMCPMC136906
OpenAlexW2152681964

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.