Cited by 327HIV Research and TreatmentHIV/AIDS drug development and treatmentVirus-based gene therapy research

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HIV DNA Integration

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Craigie, R., Bushman, F. D.·2012·Cold Spring Harbor Perspectives in Medicine

DOI 10.1101/cshperspect.a006890PMC PMC3385939

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Abstract

Retroviruses are distinguished from other viruses by two characteristic steps in the viral replication cycle. The first is reverse transcription, which results in the production of a double-stranded DNA copy of the viral RNA genome, and the second is integration, which results in covalent attachment of the DNA copy to host cell DNA. The initial catalytic steps of the integration reaction are performed by the virus-encoded integrase (IN) protein. The chemistry of the IN-mediated DNA breaking and joining steps is well worked out, and structures of IN-DNA complexes have now clarified how the overall complex assembles. Methods developed during these studies were adapted for identification of IN inhibitors, which received FDA approval for use in patients in 2007. At the chromosomal level, HIV integration is strongly favored in active transcription units, which may promote efficient viral gene expression after integration. HIV IN binds to the cellular factor LEDGF/p75, which promotes efficient infection and tethers IN to favored target sites. The HIV integration machinery must also interact with many additional host factors during infection, including nuclear trafficking and pore proteins during nuclear entry, histones during initial target capture, and DNA repair proteins during completion of the DNA joining steps. Models for some of the molecular mechanisms involved have been proposed, but important details remain to be clarified.

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HIV-1 Antiretroviral Drug TherapyPreprint
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Specific HIV integration sites are linked to clonal expansion and persistence of infected cells
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“A number of different investigators have shown that HIV-1 prefers to integrate into the introns of highly expressed genes (Craigie and Bushman, 2012).”
Background

See all 327

Authors: Craigie, R., & Bushman, F. D.
Affiliations: National Institutes of Health (US)
University of Pennsylvania (US)
ORCID: Craigie, R.
Bushman, F. D.
Venue: Cold Spring Harbor Perspectives in Medicine
Publisher: Cold Spring Harbor Laboratory
Published: 2012-05-08
Volume: 2
Issue: 7
Pages: a006890-a006890
ISSN: 2157-1422 (ISSN-L)
DOI: 10.1101/cshperspect.a006890
PMC: PMC3385939
OpenAlex: W2110488501
Cited by: 327
References: 137
Citations by year: 2026: 10 · 2025: 15 · 2024: 22 · 2023: 14 · 2022: 35 · 2021: 26 · 2020: 19 · 2019: 22 · 2018: 29 · 2017: 28 · 2016: 30 · 2015: 29 · 2014: 22 · 2013: 22 · 2012: 4
Type: posted content
Language: en
Open access: bronze
doi.org
Locations: Cold Spring Harbor Perspectives in Medicine (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Allergy and Infectious Diseases (P01AI090935)
Topics: Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Keywords: HIV integration, integrase, retroviral replication, reverse transcription, integrase inhibitors, LEDGF/p75, transcriptionally active chromatin, host factors, nuclear trafficking, histones, DNA repair, HIV gene expression
MeSH terms: Cell Nucleus, DNA, Viral, HIV, Humans, Virus Replication, Virus Integration, HIV Integrase, Intercellular Signaling Peptides and Proteins, Reverse Transcription

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