Evidence map›Paper›PMID 11134296›Full record

ArticleJournal of virology2001

Design and use of an inducibly activated human immunodeficiency virus type 1 Nef to study immune modulation.

S F Walk, M Alexander, B Maier, M L Hammarskjold, D M Rekosh, K S Ravichandran

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.2field-weighted citation impact, top 24% 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

17 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Small molecule inhibitors of the HIV-1 virulence factor, Nef.Drug discovery today. Technologies · 2013
    Review
  8. Article
  9. Article
  10. Mechanisms of HIV-1 Nef function and intracellular signaling.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2011
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. 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.

S F WalkCarter Immunology Center, Myles H. Thaler Center for AIDS and Human Retrovirus Research and the Department of Microbiology, University of Virginia, Charlottesville, Virginia 22908, USA.
M Alexander
B Maier
M L Hammarskjold
D M Rekosh
K S Ravichandran
University of Virginia · US

Funding

MECHANISMS UNDERLYING IMMUNE MODULATION BY NEFR21AI044349 · NIAID · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI REKOSH, DAVID M · 1998 to 1999
–
NIAID NIH HHS R21AI44349
6 · The paper itself

Abstract

The Nef protein of the human immunodeficiency virus type 1 (HIV-1) has been shown to enhance the infectivity of virus particles, downmodulate cell surface proteins, and associate with many intracellular proteins that are thought to facilitate HIV infection. One of the challenges in defining the molecular events regulated by Nef has been obtaining good expression of Nef protein in T cells. This has been attributed to effects of Nef on cell proliferation and apoptosis. We have designed a Nef protein that is readily expressed in T-cell lines and whose function is inducibly activated. It is composed of a fusion between full-length Nef and the estrogen receptor hormone-binding domain (Nef-ER). The Nef-ER is kept in an inactive state due to steric hindrance, and addition of the membrane-permeable drug 4-hydroxytamoxifen (4-HT), which binds to the ER domain, leads to inducible activation of Nef-ER within cells. We demonstrate that Nef-ER inducibly associates with the 62-kDa Ser/Thr kinase and is localized to specific membrane microdomains (lipid rafts) only after activation. Using this inducible Nef, we also compared the specific requirements for CD4 and HLA-A2 downmodulation in a SupT1 T-cell line. Half-maximal downmodulation of cell surface CD4 required very little active Nef-ER and occurred as early as 4 h after addition of 4-HT. In contrast, 50% downmodulation of HLA-A2 by Nef required 16 to 24 h and about 50- to 100-fold-greater concentrations of 4-HT. These data suggest that HLA-A2 downmodulation may require certain threshold levels of active Nef. The differential timing of CD4 and HLA-A2 downmodulation may have implications for HIV pathogenesis and immune evasion.

Indexed as

AnimalsCD4 AntigensCell LineDown-RegulationGene Products, nefHIV-1HLA-A2 AntigenHumansMembrane MicrodomainsMicenef Gene Products, Human Immunodeficiency Virusp21-Activated KinasesProtein Serine-Threonine KinasesProtein Structure, TertiaryReceptors, EstrogenRecombinant Fusion ProteinsafimoxifeneCD4 AntigensGene Products, nefHLA-A2 Antigennef Gene Products, Human Immunodeficiency Virusp21-Activated KinasesProtein Serine-Threonine KinasesReceptors, EstrogenRecombinant Fusion ProteinsTamoxifen

Identifiers

PMID11134296
PMCPMC113979
OpenAlexW2140728605

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.