A large nucleoprotein assembly at the ends of the viral DNA mediates retroviral DNA integration

Wei, Shui‐Qing; Mizuuchi, Kiyoshi; Craigie, Robert

doi:10.1093/emboj/16.24.7511

Cited by 102HIV Research and TreatmentVirus-based gene therapy researchT-cell and Retrovirus Studies

A large nucleoprotein assembly at the ends of the viral DNA mediates retroviral DNA integration

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Wei, Shui‐Qing, Mizuuchi, Kiyoshi, Craigie, Robert·1997·The EMBO Journal

DOI 10.1093/emboj/16.24.7511PMC PMC1170350

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Abstract

We have probed the nucleoprotein organization of Moloney murine leukemia virus (MLV) pre-integration complexes using a novel footprinting technique that utilizes a simplified in vitro phage Mu transposition system. We find that several hundred base pairs at each end of the viral DNA are organized in a large nucleoprotein complex, which we call the intasome. This structure is not formed when pre-integration complexes are made by infecting cells with integrase-minus virus, demonstrating a requirement for integrase. In contrast, footprinting of internal regions of the viral DNA did not reveal significant differences between pre-integration complexes with and without integrase. Treatment with high salt disrupts the intasome in parallel with loss of intermolecular integration activity. We show that a cellular factor is required for reconstitution of the intasome. Finally, we demonstrate that DNA-protein interactions involving extensive regions at the ends of the viral DNA are functionally important for retroviral DNA integration activity. Current in vitro integration systems utilizing purified integrase lack the full fidelity of the in vivo reaction. Our results indicate that both host factors and long viral DNA substrates may be required to reconstitute an in vitro system with all the hallmarks of DNA integration in vivo.

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Footprinting studies suggest that as much as 200-250 bp at each viral DNA end are protected by a stable protein complex within retroviral pre-integration complexes.
“Furthermore, while the intasome structure covers only ~20 bp of vDNA, footprinting studies suggested that as much as 200–250 bp at each vDNA end are protected by a stable protein complex within retroviral PICs45,46.”
From Structure and function of retroviral integrase (2022) · cites this paper as [45]
The Footprinting by Mu-mediated PCR section reports protection at each viral DNA end in pre-integration complexes and associates it with a nucleoprotein structure. But it says protection extends approximately 500 bp, with no sharply defined border, rather than only as much as 200–250 bp. No page number is available in our copy. (LLM, conf=0.88)
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Authors: Wei, S., Mizuuchi, K., & Craigie, R.
Affiliations: National Institutes of Health (US)
Corresponding author: Craigie, Robert
Venue: The EMBO Journal
Publisher: Springer Science and Business Media LLC
Published: 1997-12-15
Volume: 16
Issue: 24
Pages: 7511-7520
ISSN: 0261-4189 (ISSN-L)
1460-2075
DOI: 10.1093/emboj/16.24.7511
PMC: PMC1170350
OpenAlex: W2022750544
Cited by: 102
References: 47
Citations by year: 2026: 2 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 5 · 2014: 4 · 2013: 3 · 2012: 2
FWCI: 2.24
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: The EMBO Journal (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
Topics: Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
Keywords: retroviral integration, intasome, Moloney murine leukemia virus, preintegration complex, integrase, nucleoprotein complexes, protein-DNA interactions, host factors
MeSH terms: Animals, Base Composition, Base Sequence, DNA, DNA Transposable Elements, DNA-Binding Proteins, DNA, Viral, Molecular Sequence Data, Moloney murine leukemia virus, Nucleoproteins, Oligodeoxyribonucleotides, Bacteriophage mu, Polymerase Chain Reaction, Mutagenesis, Insertional, Virus Integration, DNA Footprinting, Mice

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A large nucleoprotein assembly at the ends of the viral DNA mediates retroviral DNA integration

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