Retroviral integration: structure of the initial covalent product and its precursor, and a role for the viral IN protein
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An essential step in the life cycle of a retrovirus is the integration of a DNA copy of the viral genome into a host cell chromosome. We have analyzed the structure of the initial covalent product of an in vitro retroviral integration reaction and determined the structure of the ends of the unintegrated linear viral DNA molecules present in vivo in cells infected with murine leukemia virus (MLV). Our results lead to the following conclusions: (i) Circularization of viral DNA plays no role in integration. The direct precursor to the integrated MLV provirus is a linear molecule. (ii) The initial step in the integration reaction is probably a cleavage that removes the terminal 2 bases from each 3' end of the viral DNA. This cleavage depends on a virally encoded protein, IN, that has previously been shown genetically to be required for integration. (iii) The resulting viral 3' ends are joined to target DNA to form the initial recombination intermediate.
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During 3′ end processing, IN removes di- or trinucleotides at both the U3 and U5 att sites downstream of the conserved CA dinucleotide, generating staggered ends.
“During this 3′ end processing, IN removes the few nucleotides (di- or trinucleotides, depending upon the retrovirus) by hydrolyzing the phosphodiester bond at both the U3 and U5 att sites downstream of the phylogenetically conserved CA dinucleotide, generating staggered ends (Fujiwara and Mizuuchi 1988, Brown et al. 1989, Roth et al. 1989).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Brown et al. 1989
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- Authors
- Brown, P. O., Bowerman, B., Varmus, H. E., & Bishop, J. M.
- Affiliations
- G. W. Hooper Research Foundation, San Francisco, CA.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1989-04
- Volume
- 86
- Issue
- 8
- Pages
- 2525-2529
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC286949
- OpenAlex
- W2058019531
- Cited by
- 399
- References
- 16
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 10 · 2021: 6 · 2020: 3 · 2019: 7 · 2018: 6 · 2017: 3 · 2016: 10 · 2015: 10 · 2014: 6 · 2013: 7 · 2012: 12
- FWCI
- 8.40
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- retroviral integration, integrase, murine leukemia virus, provirus, recombination intermediates
- MeSH terms
- Cell Transformation, Viral, DNA, Viral, Genes, Viral, Leukemia Virus, Murine, Nucleic Acid Conformation, Repetitive Sequences, Nucleic Acid, Viral Proteins, 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.
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