Distribution of targets for avian retrovirus DNA integration in vivo
Open accessAbstract
The targeting of DNA integration in retrovirus-infected cells is a central yet very poorly understood aspect of the biology of the virus. To investigate this problem, we have assessed the use of specific sites for integration targets of avian leukosis virus (ALV) DNA within defined regions of turkey embryo fibroblast (TEF) cellular DNA. For this purpose, we developed an assay of sufficient sensitivity and specificity to allow detection and location of single integration events in a population of 5 million cells. Targets selected for study were either regions cloned by virtue of a previous integration event or clones chosen at random from cellular DNA. By use of this approach, we found that all genomic regions tested contained integration targets, with a frequency that varied from approximately 0.2 to 4 times that expected for random integration. Within regions, the frequency of use of specific sites varied considerably, with some sites used up to 280 times random frequency. When one region was introduced into cells at moderately high copy number by transfection, it provided integration targets in a pattern very much like that seen with the same sequence in vitro. On the basis of our sampling, we conclude that most or all regions of the TEF genome are accessible to ALV retroviral integration. As with integration in vitro, integration specificity seems to be determined largely by local structural features rather than accessibility of specific regions.
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Depending on the retrovirus type, IN acts on approximately 16-20 terminal nucleotides of the LTR.
“Depending upon the retrovirus type, IN acts on ~16–20 terminal nucleotides of the LTR (Colicelli and Goff 1988, Withers-Ward et al. 1994, Masuda et al. 1998, Brown et al. 1999).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Withers-Ward et al. 1994
In the section on integration-site detection (page unavailable), the paper reports that the LTR’s 3′ end loses two bases during integration and joins to target DNA. That supports involvement of the LTR terminus, but our copy does not establish that IN acts on approximately 16–20 terminal nucleotides or that this length varies by retrovirus type (searched for the range, terminal sequences, and integrase activity). (LLM, conf=0.72)
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“Depending upon the retrovirus type, IN acts on ∼ 16–20 terminal nucleotides of the LTR (Colicelli and Goff 1988 , Withers-Ward et al. 1994 , Masuda et al. 1998 , Brown et al. 1999 ).”
- Authors
- Withers-Ward, E. S., Kitamura, Y., Barnes, J. P., & Coffin, J. M.
- Affiliations
- Tufts University (US)
- ORCID
- Coffin, J M
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1994-06-15
- Volume
- 8
- Issue
- 12
- Pages
- 1473-1487
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W1996628643
- Cited by
- 125
- References
- 44
- Citations by year
- 2025: 1 · 2024: 2 · 2017: 2 · 2016: 1 · 2015: 1
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Cancer Society
- National Cancer Institute
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- retroviral integration, avian leukosis virus, DNA accessibility, viral genome structure, site-specific integration
- MeSH terms
- Animals, Avian Leukosis Virus, Base Sequence, Cells, Cultured, Coturnix, DNA, Viral, Molecular Sequence Data, Repetitive Sequences, Nucleic Acid, Turkeys, Polymerase Chain Reaction, Virus Integration, Genome, Conserved Sequence, Sequence Analysis, DNA, DNA Primers
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