Evidence map›Paper›PMID 23661057›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2013

Viral DNA tethering domains complement replication-defective mutations in the p12 protein of MuLV Gag.

William M Schneider, Jonathon D Brzezinski, Sriram Aiyer, Nirav Malani, Mercedes Gyuricza, Frederic D Bushman, Monica J Roth

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

36 citing papers in PubMed, 52 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Structure and function of retroviral integrase.Nature reviews. Microbiology · 2022
    Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Evidence for Tethering of Human Cytomegalovirus Genomes to Host Chromosomes.Frontiers in cellular and infection microbiology · 2020
    Article
  14. Article
  15. Article
  16. Article
  17. Cellular and molecular mechanisms of HIV-1 integration targeting.Cellular and molecular life sciences : CMLS · 2018
    Review
  18. Article
  19. Interactions between Retroviruses and the Host Cell Genome.Molecular therapy. Methods & clinical development · 2018
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

William M SchneiderDepartment of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA.
Jonathon D Brzezinski
Sriram Aiyer
Nirav Malani
Mercedes Gyuricza
Frederic D Bushman
Monica J Roth
Rutgers, The State University of New Jersey · USUniversity of Pennsylvania · US

Funding

Favored Sites for HIV Integration in the Human GenomeR01AI052845 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI BUSHMAN, FREDERIC D · 2002 to 2017
$5.6M
Massively Parallel Analysis of Integration in Therapeutic Gene TransferR01AI082020 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI BUSHMAN, FREDERIC D · 2009 to 2018
$3.5M
Integration of Murine Retroviral VectorsR01GM070837 · NIGMS · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI ROTH, MONICA J. · 2005 to 2013
$2.1M
Retroviral Integration & HDAC inhibitorsR01GM088808 · NIGMS · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI ROTH, MONICA J. · 2009 to 2012
$1.3M
GRADUATE TRAINING IN CELLULAR AND MOLECULAR BIOLOGYT32GM008360 · NIGMS · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI MADURA, KIRAN · 1991 to 2011
$1.1M
NIAID NIH HHS AI082020NIAID NIH HHS AI52845NIAID NIH HHS R01 AI052845NIAID NIH HHS R01 AI082020NIGMS NIH HHS GM088808NIGMS NIH HHS R01 GM070837NIGMS NIH HHS R01 GM088808NIGMS NIH HHS T32 GM008360
6 · The paper itself

Abstract

The p12 protein of murine leukemia virus (MuLV) group-specific antigen (Gag) is associated with the preintegration complex, and mutants of p12 (PM14) show defects in nuclear entry or retention. Here we show that p12 proteins engineered to encode peptide sequences derived from known viral tethering proteins can direct chromatin binding during the early phase of viral replication and rescue a lethal p12-PM14 mutant. Peptides studied included segments of Kaposi sarcoma herpesvirus latency-associated nuclear antigen (LANA)(1-23), human papillomavirus 8 E2, and prototype foamy virus chromatin-binding sequences. Amino acid substitutions in Kaposi sarcoma herpesvirus LANA and prototype foamy virus chromatin-binding sequences that blocked nucleosome association failed to rescue MuLV p12-PM14. Rescue by a larger LANA peptide, LANA(1-32), required second-site mutations that are predicted to reduce peptide binding affinity to chromosomes, suggesting that excessively high binding affinity interfered with Gag/p12 function. This is supported by confocal microscopy of chimeric p12-GFP fusion constructs showing the reverted proteins had weaker association to condensed mitotic chromosomes. Analysis of the integration-site selection of these chimeric viruses showed no significant change in integration profile compared with wild-type MuLV, suggesting release of the tethered p12 post mitosis, before viral integration.

Indexed as

AnimalsAntigens, ViralBase SequenceBlotting, WesternCell LineChromatinCloning, MolecularDNA, ViralDogsFluorescence Recovery After PhotobleachingGene Products, gagGreen Fluorescent ProteinsHumansImmunoprecipitationLeukemia Virus, MurineMicroscopy, ConfocalAntigens, ViralChromatinDNA, ViralGag protein p12, moloney murine leukemia virusGene Products, gagGreen Fluorescent Proteinslatency-associated nuclear antigenNuclear Proteinsoncogene protein E2, Human papillomavirus type 8Oncogene Proteins, ViralTrans-Activatorsgammaretroviral vectorsnuclear retentionretroviral integration

Identifiers

PMID23661057
PMCPMC3677494
OpenAlexW2030853182

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.