Cited by 400HIV Research and TreatmentT-cell and Retrovirus StudiesVirus-based gene therapy research

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Retroviral integration: structure of the initial covalent product and its precursor, and a role for the viral IN protein

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Brown, P O, Bowerman, B, Varmus, H E, Bishop, J M·1989·Proceedings of the National Academy of Sciences

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Abstract

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.

Integrity signals

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Crossref · 10.1073/pnas.86.8.2525

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Development and application of non-integrating lentiviral vectors for gene therapy
Apolonia, L. (2009) · UCL Discovery (University College London)

Authors: Brown, P. O., Bowerman, B., Varmus, H. E., & Bishop, J. M.
Affiliations: G. W. Hooper Research Foundation, San Francisco, CA.
ORCID: Brown, P O
Bowerman, B
Varmus, H E
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
DOI: 10.1073/pnas.86.8.2525
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

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Retroviral integration: structure of the initial covalent product and its precursor, and a role for the viral IN protein

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