The influence of DNA and nucleosome structure on integration events directed by HIV integrase
Open accessAbstract
DNA copies of the human immunodeficiency virus (HIV) genome integrate nonrandomly into the chromosomal DNA of the host cell. In this report, we investigate the molecular basis of this selectivity using the virus-encoded HIV integrase to direct integration of a synthetic HIV long terminal repeat substrate into either DNA molecules of known structure or previously defined nucleosomal complexes. We find that the structure of the target greatly influences the site of integration, and, moreover, DNA curvature, flexibility, and rigidity in solution all influence the frequency of integration. Importantly, for DNA with all of these properties, the distortion of the double helix directed by association with the histone proteins promotes the integration reaction and alters the distribution of sites that are selected for integration. We suggest that both intrinsic DNA structure and the folding of DNA into chromosomal structures will exert a major influence on target site selection for integration of the viral genome.
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PIC or intasome have greater inclination to integrate into bent target DNA wrapped with histones or transcription factors compared to naked DNA.
“It has been observed that PIC or the intasome have greater inclination to integrate into bent target DNA that is wrapped with histones or transcription factors in comparison to the naked DNA (Müller and Varmus 1994, Pruss et al. 1994, Maskell et al. 2015, Matysiak et al. 2017).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Pruss et al. 1994
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- Authors
- Pruss, D., Reeves, R., Bushman, F. D., & Wolffe, A. P.
- Affiliations
- National Institutes of Health (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1994-10
- Volume
- 269
- Issue
- 40
- Pages
- 25031-25041
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1569658633
- Cited by
- 173
- References
- 63
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 5 · 2018: 3 · 2017: 6 · 2016: 3 · 2015: 7 · 2014: 8 · 2013: 2 · 2012: 2
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- HIV integrase, viral DNA integration, target site selection, nucleosome structure, DNA curvature, DNA flexibility, histone proteins, long terminal repeat, chromatin
- MeSH terms
- Base Sequence, DNA, DNA Nucleotidyltransferases, HIV, Molecular Sequence Data, Nucleosomes, Virus Integration, Integrases
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