Evidence map›Paper›PMID 12368302›Full record

ArticleJournal of virology2002

Nuclear localization of human immunodeficiency virus type 1 preintegration complexes (PICs): V165A and R166A are pleiotropic integrase mutants primarily defective for integration, not PIC nuclear import.

Ana Limón, Eric Devroe, Richard Lu, Hina Z Ghory, Pamela A Silver, Alan Engelman

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
3.3field-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

62 citing papers in PubMed, 96 citations in OpenAlex.

  1. Article
  2. Article
  3. Complex Relationships between HIV-1 Integrase and Its Cellular Partners.International journal of molecular sciences · 2022
    Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Retroviral DNA Integration.Chemical reviews · 2016
    Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Allosteric integrase inhibitor potency is determined through the inhibition of HIV-1 particle maturation.Proceedings of the National Academy of Sciences of the United States of America · 2013
    Article
  19. Article
  20. Article

2 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

6 authors at 2 institutions in 1 country.

Ana LimónDepartment of Pathology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Eric Devroe
Richard Lu
Hina Z Ghory
Pamela A Silver
Alan Engelman
Dana-Farber Cancer Institute · USHarvard University · US

Funding

Biochemical Mechanism of HIV DNA IntegrationR37AI039394 · NIAID · DANA-FARBER CANCER INST · PI Alan N. Engelman · 2010 to 2026
$10.2M
DFCI-BIDMC-CH CENTER FOR AIDS RESEARCHP30AI028691 · NIAID · DANA-FARBER CANCER INSTITUTE · PI SODROSKI, JOSEPH G · 1989 to 2003
$6.2M
Transport of Proteins In and Out of the NucleusR37GM036373 · NIGMS · HARVARD MEDICAL SCHOOL · PI SILVER, PAMELA A · 2003 to 2012
$4.3M
BIOCHEMICAL MECHANISM OF HIV DNA INTEGRATIONR01AI039394 · NIAID · DANA-FARBER CANCER INSTITUTE · PI ENGELMAN, ALAN N. · 1996 to 2009
$3.8M
TRANSPORT OF PROTEINS IN AND OUT OF THE NUCLEUSR01GM036373 · NIGMS · PRINCETON UNIVERSITY · PI SILVER, PAMELA A · 1986 to 2016
$2.5M
MECHANISM OF NON-INTEGRASE-MEDIATED HIV-1 REPLICATIONR01AI045313 · NIAID · DANA-FARBER CANCER INSTITUTE · PI ENGELMAN, ALAN N. · 1999 to 2001
$434k
MECHANISM OF NONINTEGRASE MEDIATED HIV1 REPLICATIONR21AI045313 · NIAID · DANA-FARBER CANCER INSTITUTE · PI ENGELMAN, ALAN N. · 1999 to 1999
–
NIAID NIH HHS AI28691NIAID NIH HHS AI39394NIAID NIH HHS AI45313NIAID NIH HHS P30 AI028691NIAID NIH HHS R01 AI039394NIAID NIH HHS R37 AI039394NIGMS NIH HHS GM36373NIGMS NIH HHS R01 GM036373NIGMS NIH HHS R37 GM036373
6 · The paper itself

Abstract

Retroviral replication requires the integration of reverse-transcribed viral cDNA into a cell chromosome. A key barrier to forming the integrated provirus is the nuclear envelope, and numerous regions in human immunodeficiency virus type 1 (HIV-1) have been shown to aid the nuclear localization of viral preintegration complexes (PICs) in infected cells. One region in integrase (IN), composed of Val-165 and Arg-166, was reportedly essential for HIV-1 replication and nuclear localization in all cell types. In this study we confirmed that HIV-1(V165A) and HIV-1(R166A) were replication defective and that less mutant viral cDNA localized to infected cell nuclei. However, we present three lines of evidence that argue against a specific role for Val-165 and Arg-166 in PIC nuclear import. First, results of transient transfections revealed that V165A FLAG-tagged IN and green fluorescent protein-IN fusions carrying either V165A or R166A predominantly localized to cell nuclei. Second, two different strains of previously described class II IN mutant viruses displayed similar nuclear entry profiles to those observed for HIV-1(V165A) and HIV-1(R166A), suggesting that defective nuclear import may be a common phenotype of replication-defective IN mutant viruses. Third, V165A and R166A mutants were defective for in vitro integration activity, when assayed both as PICs isolated from infected T-cells and as recombinant IN proteins purified from Escherichia coli. Based on these results, we conclude that HIV-1(V165A) and HIV-1(R166A) are pleiotropic mutants primarily defective for IN catalysis and that Val-165 and Arg-166 do not play a specific role in the nuclear localization of HIV-1 PICs in infected cells.

Indexed as

Virus IntegrationActive Transport, Cell NucleusCell NucleusDNA, ViralHeLa CellsHIV-1HIV IntegraseHumansJurkat CellsRecombinant Fusion ProteinsTransfectionVirus ReplicationDNA, ViralHIV IntegraseRecombinant Fusion Proteins

Identifiers

PMID12368302
PMCPMC136649
OpenAlexW2039538100

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.