Evidence map›Paper›PMID 16956949›Full record

ArticleJournal of virology2006

Human immunodeficiency virus type 1 Vpr induces DNA replication stress in vitro and in vivo.

Erik S Zimmerman, Michael P Sherman, Jana L Blackett, Jason A Neidleman, Christophe Kreis, Pamela Mundt, Samuel A Williams, Maria Warmerdam, James Kahn, Frederick M Hecht and 5 more

Open access · bronzeAbstract 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 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
3.1field-weighted citation impact, top 7% 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

76 citing papers in PubMed, 102 citations in OpenAlex.

  1. Trial
  2. Manipulation of the cell cycle by HIV-1.Biochemical Society transactions · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Emergence and molecular mechanisms of SARS-CoV-2 and HIV to target host cells and potential therapeutics.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2020
    Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

16 more citing papers are in PubMed but not listed here.

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

15 authors at 3 institutions in 1 country.

Erik S ZimmermanDivision of Cellular Biology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA.
Michael P Sherman
Jana L Blackett
Jason A Neidleman
Christophe Kreis
Pamela Mundt
Samuel A Williams
Maria Warmerdam
James Kahn
Frederick M Hecht
Robert M Grant
Carlos M C de Noronha
Andrew S Weyrich
Warner C Greene
Vicente Planelles
Gladstone Institutes · USUniversity of Utah · USSan Francisco General Hospital · US

Funding

TRAINING PROGRAM IN GENETICST32GM007464 · NIGMS · UNIVERSITY OF UTAH · PI GRUNWALD, DAVID J., STANFIELD, GILLIAN · 1985 to 2020
$6.1M
INDUCTION OF APOPTOSIS BY HIV-1 VPRR01AI049057 · NIAID · UNIVERSITY OF UTAH · PI PLANELLES, VICENTE · 2000 to 2010
$3.1M
TARGETED ONCOGENESIS AND DIABETES IN TRANSGENIC MICER01CA045234 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HANAHAN, DOUGLAS · 1987 to 2009
$2.5M
ANALYSIS OF HIV VPR ACTION IN LYMPHOID HISTOCULTURESK08AI001866 · NIAID · J. DAVID GLADSTONE INSTITUTES · PI SHERMAN, MICHAEL P · 2001 to 2002
$213k
NCI NIH HHS R01 CA045234NIAID NIH HHS K08 AI001866NIAID NIH HHS R01 AI049057NIGMS NIH HHS T32 GM007464
6 · The paper itself

Abstract

The human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) causes cell cycle arrest in G2. Vpr-expressing cells display the hallmarks of certain forms of DNA damage, specifically activation of the ataxia telangiectasia mutated and Rad3-related kinase, ATR. However, evidence that Vpr function is relevant in vivo or in the context of viral infection is still lacking. In the present study, we demonstrate that HIV-1 infection of primary, human CD4+ lymphocytes causes G2 arrest in a Vpr-dependent manner and that this response requires ATR, as shown by RNA interference. The event leading to ATR activation in CD4+ lymphocytes is the accumulation of replication protein A in nuclear foci, an indication that Vpr likely induces stalling of replication forks. Primary macrophages are refractory to ATR activation by Vpr, a finding that is consistent with the lack of detectable ATR, Rad17, and Chk1 protein expression in these nondividing cells. These observations begin to explain the remarkable resilience of macrophages to HIV-1-induced cytopathicity. To study the in vivo consequences of Vpr function, we isolated CD4+ lymphocytes from HIV-1-infected individuals and interrogated the cell cycle status of anti-p24Gag-immunoreactive cells. We report that infected cells in vivo display an aberrant cell cycle profile whereby a majority of cells have a 4N DNA content, consistent with the onset of G2 arrest.

Indexed as

DNA ReplicationAtaxia Telangiectasia Mutated ProteinsCD4-Positive T-LymphocytesCell Cycle ProteinsCell LineCells, CulturedCytopathogenic Effect, ViralDNA, ViralG2 PhaseGene Products, vprHIV-1HIV InfectionsHumansIn Vitro TechniquesMacrophagesProtein Serine-Threonine KinasesAtaxia Telangiectasia Mutated ProteinsATR protein, humanCell Cycle ProteinsDNA, ViralGene Products, vprProtein Serine-Threonine Kinasesvpr Gene Products, Human Immunodeficiency Virus

Identifiers

PMID16956949
PMCPMC1641771
OpenAlexW2054343283

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.