Evidence map›Paper›PMID 17881449›Full record

ArticleJournal of virology2007

Association of Nef with p21-activated kinase 2 is dispensable for efficient human immunodeficiency virus type 1 replication and cytopathicity in ex vivo-infected human lymphoid tissue.

Michael Schindler, Devi Rajan, Anke Specht, Carolin Ritter, Kati Pulkkinen, Kalle Saksela, Frank Kirchhoff

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

18 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. HIV-1 Nef interferes with T-lymphocyte circulation through confined environments in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2012
    Article
  8. Review
  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. Review
  12. Article
  13. PAK1 as a therapeutic target.Expert opinion on therapeutic targets · 2010
    Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. HIV-1 Nef: at the crossroads.Retrovirology · 2008
    Review
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

7 authors at 4 institutions in 2 countries.

Michael SchindlerInstitute of Virology, Universitätsklinikum, 89081 Ulm, Germany.
Devi Rajan
Anke Specht
Carolin Ritter
Kati Pulkkinen
Kalle Saksela
Frank Kirchhoff
University Hospital Ulm · DEHelsinki University Hospital · FILeibniz Institute of Virology (LIV) · DETampere University Hospital · FI

Funding

Role of specific Nef functions in AIDS pathogenesisR01AI067057 · NIAID · UNIVERSITY OF ULM · PI KIRCHHOFF, FRANK · 2006 to 2008
$558k
NIAID NIH HHS 1R01AI067057-01A2NIAID NIH HHS R01 AI067057
6 · The paper itself

Abstract

Interaction of the human immunodeficiency virus type 1 (HIV-1) Nef protein with p21-activated kinase 2 (PAK2) has been proposed to play a role in T-cell activation, viral replication, apoptosis, and progression to AIDS. However, these hypotheses were based on results obtained using Nef mutants impaired in multiple functions. Recently, it was reported that Nef residue F191 is specifically involved in PAK2 binding. However, only a limited number of Nef activities were investigated in these studies. To further evaluate the role of F191 in Nef function and to elucidate the biological relevance of Nef-PAK2 interaction, we performed a comprehensive analysis of HIV-1 Nef mutants carrying F191H and F191R mutations. We found that the F191H mutation reduces and the F191R mutation disrupts the association of Nef with PAK2. Both mutants upregulated the major histocompatibility complex II (MHC-II)-associated invariant chain and downregulated CD4, MHC-I, and CD28, although with reduced efficiency for the latter. Furthermore, the F191H/R changes neither affected the levels of interleukin-2 receptor expression and apoptosis of HIV-1-infected primary T cells nor reduced Nef-mediated induction of NFAT. Unexpectedly, the F191H change markedly reduced and the F191R mutation disrupted the ability of Nef to enhance virion infectivity in P4-CCR5 indicator cells but not in TZM-bl cells or peripheral blood mononuclear cells. Most importantly, all HIV-1 Nef mutants replicated efficiently and caused CD4+ T-cell depletion in ex vivo-infected human lymphoid tissue. Altogether, our data show that the interaction of Nef with PAK2 does not play a major role in T-cell activation, viral replication, and apoptosis.

Indexed as

Amino Acid SubstitutionAntigens, Differentiation, B-LymphocyteApoptosisCD28 AntigensCD4 AntigensCell LineCytopathogenic Effect, ViralHistocompatibility Antigens Class IHistocompatibility Antigens Class IIHIV-1HumansLymphoid TissueMutation, Missensenef Gene Products, Human Immunodeficiency VirusNFATC Transcription Factorsp21-Activated KinasesAntigens, Differentiation, B-LymphocyteCD28 AntigensCD4 AntigensHistocompatibility Antigens Class IHistocompatibility Antigens Class IIinvariant chainnef Gene Products, Human Immunodeficiency Virusnef protein, Human immunodeficiency virus 1NFATC Transcription Factorsp21-Activated KinasesReceptors, Interleukin-2

Identifiers

PMID17881449
PMCPMC2169106
OpenAlexW2132634936

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.