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Symmetrical base preferences surrounding HIV-1, avian sarcoma/leukosis virus, and murine leukemia virus integration sites
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To investigate retroviral integration targeting on a nucleotide scale, we examined the base frequencies directly surrounding cloned in vivo HIV-1, murine leukemia virus, and avian sarcoma/leukosis virus integrations. Base preferences of up to 2-fold the expected frequencies were found for three viruses, representing P values down to <10 -100 and defining what appear to be preferred integration sequences. Offset symmetry reflecting the topology of the integration reaction was found for HIV-1 and avian sarcoma/leukosis virus but not murine leukemia virus, suggesting fundamental differences in the way different retroviral integration complexes interact with host-cell DNA.
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“Briefly, there seems to be a consensus, especially noticed in the retroviral integration site alignments, that a weak pal motif is often present in the target DNA sequences that are recognized by IN (Stevens and Griffith 1996, Holman and Coffin 2005, Wu et al. 2005, Miklík et al. 2023).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Holman and Coffin 2005
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“Examination of the base frequencies directly surrounding a large number of cloned HIV-1 integration sites from infected cells also revealed a preferred integration sequence, 5 -[0]GTWACCHA[7]-3 (using standard International Union of Biochemistry mixed base codes) (18, 27).”
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“transcriptionally active regions [26] to stably integrate the proviral DNA, a reaction termed strand transfer [26,27,28,29].”
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“Retroviruses display preferences for target DNA sequences in the immediate vicinity of the integration site which appear to be virus specific, and IN may select specific sequences (10, 20).”
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Mackler, R. M., Jones, N. D., Gardner, A. M., Lopez, M. A., Howard, C. J., Fishel, R. A., & Yoder, K. E. (2019) · PLoS ONE · doi:10.1371/journal.pone.0212764 · Cited by 10
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“An algorithm based on palindromic behaviour between the frequencies of bases was formulated to explore the integration sites in HIV-1 consensus sequences (Holman and Coffin 2005; Wu et al. 2005).”
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BackgroundMethodBeyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication
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“Briefly, there seems to be a consensus, especially noticed in the retroviral integration site alignments, that a weak pal motif is often present in the target DNA sequences that are recognized by IN (Stevens and Griffith 1996 , Holman and Coffin 2005 , Wu et al. 2005 , Miklík et al. 2023 ).”
Tsuruyama, T., Nakai, T., Hiratsuka, T., Jin, G., Nakamura, T., & Yoshikawa, K. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013841 · Cited by 5
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“. By analysing a number of sequences from HIV-1, avian sarcoma-leukosis virus (ASLV) and Murine Leukaemia Virus (MLV) into human cellular DNA, a symmetrical base preference surrounding HIV-1 and ASLV integration sites has been found”
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“The IN proteins of different viruses exhibit distinct preferences for integration loci, but DNA sequence per se, does not seem to be a major determining factor [5-8].”
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Metadata
- Authors
- Holman, A. G., & Coffin, J. M.
- Affiliations
- Tufts University (US)
- Corresponding author
- Coffin, John M.
- ORCID
- Coffin, John M.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-03-31
- Volume
- 102
- Issue
- 17
- Pages
- 6103-6107
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1087937
- OpenAlex
- W2026422480
- Cited by
- 164
- References
- 12
- Citations by year
- 2026: 1 · 2025: 4 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 6 · 2018: 3 · 2017: 6 · 2016: 17 · 2015: 11 · 2014: 7 · 2013: 7 · 2012: 12
- FWCI
- 4.88
- Type
- journal article
- Language
- en
- Update notices
- correction (2005-04-26)
- Open access
- green
- dx.doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Cancer Society
- F. M. Kirby Foundation
- University of Pennsylvania
- James N. Kirby Foundation
- National Institutes of Health (NIH T32)
- National Human Genome Research Institute
- National Cancer Institute (T32 CA65441, T32CA065441, R01-CA-92192, R01CA092192)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Keywords
- retroviral integration, integration site selection, HIV-1, murine leukemia virus, host cell DNA, sequence symmetry
- MeSH terms
- Alpharetrovirus, Base Composition, Base Sequence, Cloning, Molecular, HeLa Cells, Humans, HIV-1, Virus Integration
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