Evidence map›Paper›PMID 35304442›Full record

ArticleNature communications2022

A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats.

Shelby Winans, Hyun Jae Yu, Kenia de Los Santos, Gary Z Wang, Vineet N KewalRamani, Stephen P Goff

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 21% 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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.

  1. Pooled it
  2. NK-like and networked CD8bioRxiv : the preprint server for biology · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Complex Relationships between HIV-1 Integrase and Its Cellular Partners.International journal of molecular sciences · 2022
    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

6 authors at 4 institutions in 1 country.

Shelby WinansDepartment of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, NY, USA.
Hyun Jae YuBasic Science Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD, USA.
Kenia de Los SantosDepartment of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, NY, USA.
Gary Z WangDepartment of Pathology, Columbia University Medical Center, New York, NY, USA.
Vineet N KewalRamaniBasic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.ORCID http://orcid.org/0000-0002-3263-4257
Stephen P GoffDepartment of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, NY, USA. spg1@cumc.columbia.edu.ORCID http://orcid.org/0000-0002-9679-0582
Howard Hughes Medical Institute · USColumbia University Irving Medical Center · USFrederick National Laboratory for Cancer Research · USLeidos (United States) · US

Funding

The role of CPSF6 in HIV-1 infectionZIABC010487 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KEWALRAMANI, VINEET N · 2009 to 2025
$13.0M
New Animal Models to Study HIV-1 Pathogenesis, Therapy, and ReservoirsZIABC010488 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KEWALRAMANI, VINEET N · 2009 to 2025
$5.2M
Mechanisms of Silencing of Retroviral DNAs in Embryonic Cell LinesR01CA030488 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI GOFF, STEPHEN PAINE · 1985 to 2024
$4.3M
Role of Chromatin Associated Host Factors in Regulation of Retroviral ReplicationF32AI149989 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI WINANS, SHELBY JANEL · 2020 to 2020
$33k
Howard Hughes Medical InstituteNCI NIH HHS R01 CA030488NIAID NIH HHS F32 AI149989
6 · The paper itself

Abstract

Retroviruses utilize the viral integrase (IN) protein to integrate a DNA copy of their genome into host chromosomal DNA. HIV-1 integration sites are highly biased towards actively transcribed genes, likely mediated by binding of the IN protein to specific host factors, particularly LEDGF, located at these gene regions. We here report a substantial redirection of integration site distribution induced by a single point mutation in HIV-1 IN. Viruses carrying the K258R IN mutation exhibit a high frequency of integrations into centromeric alpha satellite repeat sequences, as assessed by deep sequencing, a more than 10-fold increase over wild-type. Quantitative PCR and in situ immunofluorescence assays confirm this bias of the K258R mutant virus for integration into centromeric DNA. Immunoprecipitation studies identify host factors binding to IN that may account for the observed bias for integration into centromeres. Centromeric integration events are known to be enriched in the latent reservoir of infected memory T cells, as well as in elite controllers who limit viral replication without intervention. The K258R point mutation in HIV-1 IN is also present in databases of latent proviruses found in patients, and may reflect an unappreciated aspect of the establishment of viral latency.

Indexed as

HIV IntegrasePoint MutationCentromereHumansProvirusesVirus IntegrationVirus ReplicationHIV Integrasep31 integrase protein, Human immunodeficiency virus 1

Identifiers

PMID35304442
PMCPMC8933506
OpenAlexW4221108725

What OpenQuestion holds

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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.