Evidence map›Paper›PMID 35074917›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2022

CHAF1A/B mediate silencing of unintegrated HIV-1 DNAs early in infection.

Franziska K Geis, Yosef Sabo, Xiao Chen, Yinglu Li, Chao Lu, Stephen P Goff

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.0field-weighted citation impact, top 11% 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

19 citing papers in PubMed, 28 citations in OpenAlex.

  1. NAT10/acProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Review
  3. The Role of Chaf1b in Maintaining Glioma Stem Cell Stemness and Regulating Microglial Polarization.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
  4. Unintegrated HIV-1 DNA recruits cGAS via its histone-binding domain to escape innate immunity.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Capsid-host interactions for HIV-1 ingress.Microbiology and molecular biology reviews : MMBR · 2023
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. 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 2 institutions in 1 country.

Franziska K GeisDepartment of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, NY 10032.
Yosef SaboAaron Diamond AIDS Research Center, Columbia University Medical Center, New York, NY 10032.
Xiao ChenDepartment of Genetics and Development, Columbia University Medical Center, New York, NY 10032.ORCID 0000-0001-5059-8846
Yinglu LiDepartment of Genetics and Development, Columbia University Medical Center, New York, NY 10032.
Chao LuDepartment of Genetics and Development, Columbia University Medical Center, New York, NY 10032.
Stephen P GoffDepartment of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, NY 10032; spg1@cumc.columbia.edu.ORCID 0000-0002-9679-0582
Aaron Diamond AIDS Research Center · USColumbia University Irving Medical Center · US

Funding

Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3M
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
Regulation and Function of Histone H3K36 Methylation in Mammalian ChromatinR35GM138181 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LU, CHAO · 2020 to 2024
$2.0M
NCI NIH HHS P30 CA013696NCI NIH HHS R01 CA030488NIGMS NIH HHS R35 GM138181
6 · The paper itself

Abstract

Early events of the retroviral life cycle are the targets of many host restriction factors that have evolved to prevent establishment of infection. Incoming retroviral DNAs are transcriptionally silenced before integration in most cell types, and efficient viral gene expression occurs only after formation of the provirus. The molecular machinery for silencing unintegrated retroviral DNAs of HIV-1 remains poorly characterized. Here, we identified the histone chaperones CHAF1A and CHAF1B as essential factors for silencing of unintegrated HIV-1 DNAs. Using RNAi-mediated knockdown (KD) of multiple histone chaperones, we found that KD of CHAF1A or CHAF1B resulted in a pronounced increase in expression of incoming viral DNAs. The function of these two proteins in silencing was independent of their interaction partner RBBP4. Viral DNA levels accumulated to significantly higher levels in CHAF1A KD cells over controls, suggesting enhanced stabilization of actively transcribed DNAs. Chromatin immunoprecipitation assays revealed no major changes in histone loading onto viral DNAs in the absence of CHAF1A, but levels of the H3K9 trimethylation silencing mark were reduced. KD of the H3K9me3-binding protein HP1γ accelerated the expression of unintegrated HIV-1 DNAs. While CHAF1A was critical for silencing HIV-1 DNAs, it showed no role in silencing of unintegrated retroviral DNAs of mouse leukemia virus. Our study identifies CHAF1A and CHAF1B as factors involved specifically in silencing of HIV-1 DNAs early in infection. The results suggest that these factors act by noncanonical pathways, distinct from their histone loading activities, to mediate silencing of newly synthesized HIV-1 DNAs.

Indexed as

DNA, ViralVirus IntegrationChromatin Assembly Factor-1Gene Expression Regulation, ViralGene SilencingHistonesHIV-1HIV InfectionsHost-Pathogen InteractionsHumansProvirusesTranscription, GeneticTripartite Motif-Containing Protein 28CHAF1A protein, humanCHAF1B protein, humanChromatin Assembly Factor-1DNA, ViralHistonesTripartite Motif-Containing Protein 28CHAF1Ahistone chaperonesHIV-1retroviral DNAstranscriptional silencing

Identifiers

PMID35074917
PMCPMC8795523
OpenAlexW4210573463

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.