The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
LEDGF/p75 functions downstream from preintegration complex formation to effect gene-specific HIV-1 integration
Open accessAbstract
LEDGF/p75 directly interacts with lentiviral integrase proteins and can modulate their enzymatic activities and chromosomal association. A novel genetic knockout model was established that allowed us for the first time to analyze HIV-1 integration in the absence of LEDGF/p75 protein. Supporting a crucial role for the cofactor in viral replication, HIV-1 vector integration and reporter gene expression were significantly reduced in LEDGF-null cells. Yet, integrase processed the viral cDNA termini normally and maintained its local target DNA sequence preference during integration. Preintegration complexes extracted from knockout cells moreover supported normal levels of DNA strand transfer activity in vitro. In contrast, HIV-1 lost its strong bias toward integrating into transcription units, displaying instead increased affinity for promoter regions and CpG islands. Our results reveal LEDGF/p75 as a critical targeting factor, commandeering lentiviruses from promoter- and/or CpG island-proximal pathways that are favored by other members of Retroviridae . Akin to yeast retrotransposons, disrupting the lentiviral targeting mechanism significantly perturbs overall integration.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The genic proviruses that did form under these conditions uncharacteristically congregated around transcription start sites87,99–101.”
From Structure and function of retroviral integrase (2022) · cites this paper as [99]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Knockout of the PSIP1 gene, which encodes for LEDGF/p75, similarly suppressed levels of vDNA integration in cells several fold98,99.”
From Structure and function of retroviral integrase (2022) · cites this paper as [99]
The cited source says what the claim attributes to it.
In the citing paper
“Alterations that disrupted LEDGF/p75 binding to chromatin or IN ablated its cofactor function during HIV-1 infection99,103,112.”
From Structure and function of retroviral integrase (2022) · cites this paper as [99]
The cited source says what the claim attributes to it.
In the citing paper
“However, while LEDGF/p75 is critical, it is not strictly essential for HIV-1 integration and replication. This assertion is supported by the fact that HIV-1 was able to replicate, albeit at a much-reduced level, in LEDGF knockdown cells, and the replication could be restored upon expression of LEDGF/p75 (Llano et al. 2006, Shun et al. 2007).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Shun et al. 2007
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
HIV-1 Integration in the Human Genome Favors Active Genes and Local Hotspots
Schröder, A. R. W., Shinn, P., Chen, H., Berry, C., Ecker, J. R., & Bushman, F. (2002) · Cell · doi:10.1016/s0092-8674(02)00864-4 · Cited by 1,832
Transcription Start Regions in the Human Genome Are Favored Targets for MLV Integration
Wu, X., Li, Y., Crise, B., & Burgess, S. M. (2003) · Science · doi:10.1126/science.1083413 · Cited by 1,305
Retroviral DNA Integration: ASLV, HIV, and MLV Show Distinct Target Site Preferences
Mitchell, R., Beitzel, B. F., Schröder, A. R. W., Shinn, P., Chen, H., Berry, C. C., Ecker, J. R., & Bushman, F. D. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020234 · Cited by 1,002
Deininger, P. L., & Batzer, M. A. (1999) · Molecular Genetics and Metabolism · doi:10.1006/mgme.1999.2864 · Cited by 911
Inducible gene targeting in mice using the Cre/lox system.
Sauer, B. (1998) · Methods · doi:10.1006/meth.1998.0593 · Cited by 858
HIV-1 Integrase Forms Stable Tetramers and Associates with LEDGF/p75 Protein in Human Cells
Cherepanov, P., Maertens, G., Proost, P., Devreese, B., Van Beeumen, J., Engelborghs, Y., De Clercq, E., & Debyser, Z. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209278200 · Cited by 704
Self-citationA role for LEDGF/p75 in targeting HIV DNA integration
Ciuffi, A., Llano, M., Poeschla, E., Hoffmann, C., Leipzig, J., Shinn, P., Ecker, J. R., & Bushman, F. (2005) · Nature Medicine · doi:10.1038/nm1329 · Cited by 658
HIV-1 DNA integration: Mechanism of viral DNA cleavage and DNA strand transfer
Engelman, A., Mizuuchi, K., & Craigie, R. (1991) · Cell · doi:10.1016/0092-8674(91)90297-c · Cited by 655
Self-citationAn essential role for LEDGF/p75 in HIV integration
Llano, M., Saenz, D. T., Meehan, A., Wongthida, P., Peretz, M., Walker, W. H., Teo, W., & Poeschla, E. M. (2006) · Science · doi:10.1126/science.1132319 · Cited by 537
Breaking barriers to transcription elongation
Saunders, A., Core, L. J., & Lis, J. T. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1981 · Cited by 525
Flagged first, then by citations
Cited by
Sorted by citations
Items 401–470 of 470
Lagadec, F., Singh, P. K., Calmels, C., Lapaillerie, D., Lindemann, D., Parissi, V., Cherepanov, P., Engelman, A., & Lesbats, P. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf449 · Cited by 1
Self-citationMoloney murine leukemia virus integrase and reverse transcriptase interact with PML proteins
Okino, Y., Inayoshi, Y., Kojima, Y., Kidani, S., Kaneoka, H., Honkawa, A., Higuchi, H., Nishijima, K.-I., Miyake, K., & Iijima, S. (2012) · The Journal of Biochemistry · doi:10.1093/jb/mvs063 · Cited by 1
LEDGF/p75 Deficiency Increases Deletions at the HIV-1 cDNA Ends
Bueno, M. T. D., Reyes, D., & Llano, M. (2017) · Viruses · doi:10.3390/v9090259 · Cited by 1
Ubiquitination and SUMOylation in HIV Infection: Friends and Foes
Colomer-Lluch, M., Castro‐Gonzalez, S., & Serra-Moreno, R. (2019) · Caister Academic Press eBooks · doi:10.21775/9781912530120.24 · Cited by 1
Retroviral Vectors for Gene Therapy of Monogenic Diseases
Yoder, K. E., Rabe, A. J., & Larue, R. C. (2022) · Springer eBooks · doi:10.1007/978-3-030-93333-3_7 · Cited by 1
Resistance to Inhibitors of HIV‐1 Integrase
Hombrouck, A., Clayton, R., Voet, A. R. D., Witvrouw, M., & Debyser, Z. (2011) · Wiley eBooks · doi:10.1002/9781118015377.ch30 · Cited by 1
Molecular Mechanisms of HIV-1 Infection in Neonatal Target Cells
Ahmad, N. (2012) · Future Virology · doi:10.2217/fvl.12.26 · Cited by 1
Physical Principles of Retroviral Integration in the Human GenomePreprint
Michieletto, D., Lusic, M., Marenduzzo, D., & Orlandini, E. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/247437 · Cited by 1
The mouse mammary tumor virus intasome exhibits distinct dynamics on target DNAPreprint
Baltierra‐Jasso, L. E., Jones, N. D., Ballandras-Colas, A., Engelman, A., Fishel, R. A., & Yoder, K. E. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.11.17.468995 · Cited by 1
Self-citationWellensiek, B. P. (2007) · UA Campus Repository (The University of Arizona) · Cited by 1
DNA Damage Response Proteins Are Involved in the Formation of Defective HIV-1 ProvirusesPreprint
Michalek, K., Bhattacharjee, S., Movasati, A., Clerc, V., Andres, J., Hotz, A. L., Rodrigues, D., & Metzner, K. J. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.03.31.715508 · Cited by 1
Identification of specific phylogenetic properties of HIV-1 M and O integrases
Toccafondi, E. (2022) · theses.fr (ABES) · doi:10.70675/2facab6ezc20az472dz8350z9fb6e718e1d4 · Cited by 1
Vandekerckhove, L., Christ, F., Debyser, Z., Owen, A., Back, D. J., Voet, A. R. D., Schapiro, J., & Vogelaers, D. (2014) · ASM Press eBooks · doi:10.1128/9781555815493.ch5 · Cited by 1
Madlala, P. (2011) · ResearchSpace (University of KwaZulu-Natal)
Voet, A. R. D., Maeyer, M. D., Christ, F., & Debyser, Z. (2011) · Methods and principles in medicinal chemistry · doi:10.1002/9783527635955.ch3
Engineering the Human Genome: Reflections on the Beginning
Bushman, F. D. (2014) · Human Gene Therapy · doi:10.1089/hum.2014.2524 · Cited by 1
Studies of Fv1 binding and restriction
Li, H. L. W. (2015) · UCL Discovery (University College London)
Structural aspects of Lentiviral Integrase–LEDGF Interaction
Hare, S., Engelman, A., & Cherepanov, P. (2011) · Wiley eBooks · doi:10.1002/9781118015377.ch10
Self-citationAhmed, F., Smith, J. A., Lisanti, M. P., & Daniel, R. (2011) · InTech eBooks · doi:10.5772/23016
Reis, L. C. J. (2012) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.60.2012.tde-26022013-092913
Brandano, L. A. (2011) · The Journal of the American Medical Association (JAMA) Network (American Medical Association) · doi:10.13028/5zmj-9x81
卓哉, 多. (2014) · Institutional Repositories DataBase (IRDB) · doi:10.15083/00006504
Control of HIV-1C Replication Both in Vivo and in Vitro
Xie, W. (2015) · Digital Access to Scholarship at Harvard (DASH) (Harvard University)
Mapping of HIV-1 integrase preferences for target site selection with various oligonucleotides
Snášel, J., Rosenberg, I., Pačes, O., & Pichová, I. (2009) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2009.06.012
Inhibiting HIV-1 using RNA interference (RNAi) to target novel HIV dependency factors (HDFs)
Blondeel, M. D. (2010) · University of the Witwatersrand, Johannesburg Institutional Repository on DSpace (University of the Witwatersrand, Johannesburg)
The influence of genetic variation in PSIP1 on HIV-1 infectivity in black South Africans
Gentle, N. L. (2010) · University of the Witwatersrand, Johannesburg Institutional Repository on DSpace (University of the Witwatersrand, Johannesburg)
Shazia, S. (2014) · Research Archive of Indian Institute of Technology Hyderabad (Indian Institute of Technology Hyderabad)
Host Cell Factors in HIV-1 Replication Cycle
Boso, G. (2014) · University of Minnesota Digital Conservancy (University of Minnesota)
Pickford, C., Chaltin, P., Westby, M., Debyser, Z., Desimmie, B. A., Marchand, A., Frauke, C., Shaw, S. M., & Demeulemeester, J. (2012)
Foamy virus vector integration and application in gene therapy
Sweeney, N. P. (2015) · Spiral (Imperial College London) · doi:10.25560/50704
Greene, W. C., Peterlin, B. M., & Stremlau, M. H. (2012) · Elsevier eBooks · doi:10.1016/b978-1-4557-0695-2.00003-1
An improved lentivirus vector for safer transgene integration and protein transduction
Schenkwein, D. (2013) · UEF eRepo (University of Eastern Finland)
Recent Progress in Understanding the Mechanism and Consequences of Retrotransposon Movement
Garfinkel, D. J., & Purzycka, K. J. (2017) · MDPI eBooks · doi:10.3390/books978-3-03842-541-0
Next-Generation Sequencing Techniques to Study HIV-1 Transcription and RNA Structure
Tomezsko, P. J. (2020) · Digital Access to Scholarship at Harvard (DASH) (Harvard University)
The KT Jeang Retrovirology prize 2021: Peter Cherepanov
Editorial, R. (2021) · Retrovirology · doi:10.1186/s12977-021-00573-1
Rabe, A. J., Russo, J. A., Larue, R. C., & Yoder, K. E. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.09.19.508505
Why do histone monomethylation and dimethylation cause a significant difference in binding to LEDGF?
SUZUKI, H., Okumura, H., & Itoh, S. (2025) · The Journal of Chemical Physics · doi:10.1063/5.0259337
Tocco, G., Laus, A., Casula, M., Caboni, P., Beutler, J. A., Tramontano, E., & Esposito, F. (2025) · Molecules · doi:10.3390/molecules30244709
Identification and evaluation of inhibitors targeting the HIV-1 integrase-LEDGF/p75 interaction
Harrison, A. T. (2014) · University of the Witwatersrand, Johannesburg Institutional Repository on DSpace (University of the Witwatersrand, Johannesburg)
Wells, D., Guo, S., Shao, W., Bale, M. J., Coffin, J. M., Hughes, S. H., & Wu, X. (2020) · Figshare · doi:10.6084/m9.figshare.11960178
Self-citationDebusschere, L., Bentea, E., Iglesias-Herrero, C., Peredo, N., Belle, S. V., der Veken, N. J. V., Janer, A. B., Plessers, D., Peelaerts, W., Hannes, W., et al. (2026) · Acta Neuropathologica Communications · doi:10.1186/s40478-025-02216-4
Retroviral intasome architecture shapes the dynamics of target DNA search and integration
Baltierra‐Jasso, L. E., Larue, R. C., Jones, N. D., Tan, Y. Y., Messer, R. K., Ballandras-Colas, A., Engelman, A., Fishel, R. A., & Yoder, K. E. (2026) · PLoS Pathogens · doi:10.1371/journal.ppat.1014070
Self-citationEtude des mécanismes contrôlant la spécificité d'encapsidation des ARN dans le VIH-1
Didierlaurent, L. (2010) · theses.fr (ABES) · doi:10.70675/6af45cb6z95b9z414cz94fbzdcd9c17fde4a
Analyse des réponses cellulaires induites par l’intégration d’un ADN étranger au sein du génome
Gay, V. (2010) · theses.fr (ABES) · doi:10.70675/7c4ae339z19ddz46b4zbd54zc859435d8459
Interactions between primate lentiviral capsids and heterologous cellular host factors
Mamede, J. I. (2012) · theses.fr (ABES) · doi:10.70675/e3f4366bzb31fz4382z8f0cz19483f12bfe7
Étude comparative des processus intégratifs des rétrovirus aviaires et porcins
Andary, E. A. (2011) · theses.fr (ABES) · doi:10.70675/ae4a827fzcf7az49d6zb25ez334c2c0d5829
HIV-1 Integrase During the Time: History of Drugs and Effort for the New Inhibitors’ Identification
Esposito, F., Saccoliti, F., Patacchini, E., & Santo, R. D. (2026) · Topics in medicinal chemistry · doi:10.1007/7355_2026_180
Antagonism of HUSH restriction by lentiviral Vpx and Vpr proteins
Chougui, G. (2018) · theses.fr (ABES) · doi:10.70675/a8f60021z4ac1z485az94c1za6a503874720
Identification de facteurs cellulaires régulant la rétrotransposition de Ty1 chez S. cerevisiae
Barkova, A. (2019) · theses.fr (ABES) · doi:10.70675/d3dce78az48e8z4209zb2afzd31c32c110b1
Mécanisme moléculaire de l'antagonisme du complexe HUSH par les protéines lentivirales Vpx et Vpr
Martin, M. M. (2021) · theses.fr (ABES) · doi:10.70675/eba7934fzf9faz4427zb0f8zfba715ee98c9
Rôle des partenaires de CTIP2 dans la latence post-intégrative du VIH-1 : importance de la voie SUMO
Assche, J. V. (2022) · theses.fr (ABES) · doi:10.70675/3cb6a549ze973z487dz98f4z6fbf5991098c
Said, M. A. (2023) · theses.fr (ABES) · doi:10.70675/a9c4a87dz9e77z48d7zbd35z5893bdb5df28
HIV-2 infection as a comparative lens for functional HIV-1 remission
Arthur, S. E., Atanniba, J., Nartey, P. A., Tay, Y. A., Attoh, D. A., Abana, C. Z.-Y., Bonney, E. Y., & Kyei, G. B. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1825935
The LEDGIN GS-9822 inhibits HIV-2 infection and enhances HIV-2 latency
Bruggemans, A., Vansant, G., Pellaers, E., de Velde, P. V., Christ, F., & Debyser, Z. (2026) · Microbiology Spectrum · doi:10.1128/spectrum.01699-25
HTLV-1 intasome recruits the PP2A-B56 holoenzyme and restricts its phosphatase activityPreprint
Minnell, J. J., Punch, E. K., Vanzo, T., Safari, R., Cronin, N., Cherepanov, P. G., & Maertens, G. N. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.01.722153
Self-citationSaccoliti, F., Patacchini, E., Cara, E., Zarbo, L., Messore, A., Albano, A., Ruggieri, G., Madia, V. N., Scipione, L., Costi, R., et al. (2026) · ChemMedChem · doi:10.1002/cmdc.70428
LEDGF/p75 Mediates Chemoresistance in Leukemia in a Context Dependent Manner
Akele, M. Z., Iglesias-Herrero, C., Belle, S. V., Pretto, S., Christ, F., & Debyser, Z. (2026) · Cells · doi:10.3390/cells15201866
BindingDB (2020) · UC San Diego · doi:10.7270/q2pc352q
Singh, P. (2026) · Harvard Dataverse · doi:10.7910/dvn/udt6uc
BindingDB Entry 50006022: Inhibiting the HIV integration process: past, present, and the future.
BindingDB (2020) · UC San Diego · doi:10.7270/q2qc06gp
Retroviral_integration_sites_distribution_across_gene_length.R
Singh, P. (2023) · Harvard Dataverse · doi:10.7910/dvn/au3kyv
Processed HIV-1 integration site datasets from Jurkat cells with capsid mutants
Singh, P. (2026) · Harvard Dataverse · doi:10.7910/dvn/xrkmnr
Jang, S., Radhakrishnan, R., Greenwood, J., Singh, P. K., Bedwell, G. J., Robles‐Sikisaka, R., Routh, A. L., & Engelman, A. (2026) · mBio · doi:10.1128/mbio.02276-26
Self-citation
Metadata
- Authors
- Shun, M.-C., Raghavendra, N. K., Vandegraaff, N., Daigle, J. E., Hughes, S., Kellam, P., Cherepanov, P., & Engelman, A.
- Affiliations
- Harvard University (US)
- Imperial College London (GB)
- University College London (GB)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2007-07-15
- Volume
- 21
- Issue
- 14
- Pages
- 1767-1778
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC1920171
- OpenAlex
- W2106494657
- Cited by
- 467
- References
- 61
- Citations by year
- 2026: 13 · 2025: 11 · 2024: 11 · 2023: 13 · 2022: 26 · 2021: 24 · 2020: 13 · 2019: 17 · 2018: 18 · 2017: 24 · 2016: 26 · 2015: 32 · 2014: 37 · 2013: 26 · 2012: 32
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Institutes of Health
- Medical Research Council
- National Institute of Allergy and Infectious Diseases (AI39394, R01AI039394, R37AI039394)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Keywords
- LEDGF/p75, HIV-1 integration, preintegration complex, CpG islands, DNA strand transfer, retroviral replication
- MeSH terms
- Animals, Base Sequence, Binding Sites, Cell Line, DNA, Humans, Leukemia Virus, Murine, Promoter Regions, Genetic, Transcription Factors, HIV-1, Consensus Sequence, Virus Integration, Gene Deletion, CpG Islands, Integrases, Intercellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Mice, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
