Evidence map›Paper›PMID 16415008›Full record

ArticleJournal of virology2006

Dynamic evolution of the human immunodeficiency virus type 1 pathogenic factor, Nef.

Eduardo O'Neill, Lillian S Kuo, John F Krisko, Diana R Tomchick, J Victor Garcia, John L Foster

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 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
2.5field-weighted citation impact, top 10% 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, 76 citations in OpenAlex.

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  18. A combinatorial approach to the design of vaccines.Journal of mathematical biology · 2015
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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 2 institutions in 1 country.

Eduardo O'NeillDepartment of Internal Medicine, Division of Infectious Diseases Y9.206, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390-9113, USA.
Lillian S Kuo
John F Krisko
Diana R Tomchick
J Victor Garcia
John L Foster
Office of Infectious Diseases · USThe University of Texas Southwestern Medical Center · US

Funding

NEF FUNCTIONR01AI033331 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI GARCIA-MARTINEZ, J. VICTOR · 1994 to 2010
$4.4M
NIAID NIH HHS AI 33331NIAID NIH HHS R01 AI033331
6 · The paper itself

Abstract

The human immunodeficiency virus type 1 (HIV-1) early gene product Nef is a multifunctional protein that alters numerous pathways of T-cell function, including endocytosis, signal transduction, vesicular trafficking, and immune modulation, and is a major determinant of pathogenesis. Individual Nef functions include PAK-2 activation, CD4 downregulation, major histocompatibility complex (MHC) class I downregulation, and enhancement of viral particle infectivity. How Nef accomplishes its multiple tasks presents a difficult problem of mechanistic analysis because of the complications associated with multiple, overlapping functional domains in the context of significant sequence variability. To address these issues we determined the conservation of each Nef residue based on 1,643 subtype B Nef sequences. Mutational analysis based on conservative substitutions and Nef sequence data allowed us to search for amino acids on the surface of Nef that are specifically required for PAK-2 activation. We found residues 85, 89, and 191 to be highly significant determinants for Nef's PAK-2 activation function but functionally unlinked to CD4 and MHC class I downregulation or enhancement of infectivity. These residues are not conserved across HIV-1 subtypes but are confined to separate sets of surface elements within a subtype. Thus, L85/H89/F191 and F85/F89/R191 are dominant in subtype B and subtype E or C, respectively. Our results provide support for developing subtype-specific interventions in HIV-1 disease.

Indexed as

Evolution, MolecularAmino Acid SequenceAmino Acid SubstitutionCell LineConserved SequenceDatabases, ProteinEnzyme ActivationGene Products, nefHeLa CellsHIV-1HumansIn Vitro TechniquesMutagenesis, Site-Directednef Gene Products, Human Immunodeficiency Virusp21-Activated KinasesProtein Serine-Threonine KinasesGene Products, nefnef Gene Products, Human Immunodeficiency Virusp21-Activated KinasesPAK2 protein, humanProtein Serine-Threonine KinasesRecombinant Proteins

Identifiers

PMID16415008
PMCPMC1346962
OpenAlexW2158099800

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.