Retroviral DNA integration: structure of an integration intermediate

Fujiwara, Tamio; Mizuuchi, Kiyoshi

doi:10.1016/0092-8674(88)90071-2

Cited by 388T-cell and Retrovirus StudiesVirus-based gene therapy researchHIV Research and Treatment

Retroviral DNA integration: structure of an integration intermediate

Fujiwara, Tamio, Mizuuchi, Kiyoshi·1988·Cell

DOI 10.1016/0092-8674(88)90071-2

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Abstract

The structure of a presumptive DNA intermediate in the integration of retroviral DNA was studied in a cell-free reaction with exogenously added target DNA. The product made by viral core particles of Moloney murine leukemia virus (Mo-MLV) containing linear viral DNA has a structure consistent with an integration mechanism similar to that observed during bacteriophage Mu transposition. In this intermediate, the 3' ends of the LTR sequences are joined to the target DNA, while the 5' ends of the viral DNA remain unjoined. The 5' ends of the LTR sequences in the intermediate are exactly the same as those found in the unintegrated linear double-stranded viral DNA. This result demonstrates that the linear form of Mo-MLV DNA can integrate directly without prior circularization.

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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 Fujiwara and Mizuuchi 1988
PIC-containing reverse-transcribed dsDNA can be integrated into heterologous DNA in vitro.
“These studies demonstrated that PIC-containing reverse-transcribed dsDNA could be integrated into a heterologous DNA (Fujiwara and Mizuuchi 1988, Fujiwara and Craigie 1989, Bushman et al. 1990, Craigie et al. 1990, Katz et al. 1990, Lee and Coffin 1990, Engelman et al. 1991, Brown 1997).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Fujiwara and Mizuuchi 1988
The intasome containing processed viral DNA attaches to host cell DNA, facilitating staggered cleavage of host DNA by IN using viral DNA 3′-hydroxyls as nucleophiles.
“Secondly, the intasome containing the processed viral DNA attaches to the host cell DNA, which facilitates the cleavage of the host cell DNA in a staggered fashion by IN using viral DNA 3′-hydroxyls as nucleophiles (Fujiwara and Mizuuchi 1988, Bushman and Craigie 1991, Engelman et al. 1991).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Fujiwara and Mizuuchi 1988

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Authors: Fujiwara, T., & Mizuuchi, K.
Affiliations: National Institutes of Health (US)
ORCID: Mizuuchi, Kiyoshi
Venue: Cell
Publisher: Elsevier BV
Published: 1988-08
Volume: 54
Issue: 4
Pages: 497-504
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/0092-8674(88)90071-2
OpenAlex: W1992073293
Cited by: 385
References: 34
Citations by year: 2025: 4 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 5 · 2017: 5 · 2016: 4 · 2015: 7 · 2014: 5 · 2013: 5 · 2012: 10
FWCI: 14.83
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
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 › Immunology and Microbiology › Virology › HIV Research and Treatment
Keywords: retroviral integration, Moloney murine leukemia virus, long terminal repeat, target DNA
MeSH terms: Cell-Free System, DNA, Recombinant, DNA, Viral, Moloney murine leukemia virus, Retroviridae

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Retroviral DNA integration: structure of an integration intermediate

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