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

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

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

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

Registry

Crossref · 10.1073/pnas.86.8.2525

Cites

16 of 16 references verified0 citation errors · 0 not checkable

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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).”

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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
Published
1989-04
Volume
86
Issue
8
Pages
2525-2529
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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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