HIV 2-long terminal repeat circular DNA is stable in primary CD4+T Cells
Open accessAbstract
Treatment resistant latent reservoirs remain a barrier to cure HIV, but the maintenance and properties of these reservoirs are not completely understood. 2-LTR circular HIV DNA has been used to assess ongoing viral replication in HAART treated patients. However, the half-life of this DNA form is still debated with conflicting in vivo and in vitro data. Prior in vitro studies have focused on cell lines or short lived activated cells in cultures of brief duration, while in vivo studies have the added complications of cell migration, division, and death. Therefore, we monitored the stability of 2-LTR circles in primary CD4+T cells in a month long culture and compared it to the stability of integrated HIV DNA and T cell receptor excision circles (TRECs), another circular DNA form that is thought to be stable. We found that 2-LTRs, along with TRECs, were stable, suggesting 2-LTRs do not necessarily indicate ongoing replication.
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The additional DNA fragments did not emerge via circular LTR integration because circular LTR viral genome configuration was absent in parental U1 cells and is short lived and intolerant to repeated passaging.
“The additional fragments did not emerge via circular LTR integration, because it was absent in the parental U1 cells, and such circular LTR viral genome configuration occurs immediately after HIV-1 infection but is short lived and intolerant to repeated passaging”
From RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection (2014) · cites this paper as [20]
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Mechanisms of HIV-1 Persistence and Post-Treatment Control
Sharaf, R. R. (2019) · Digital Access to Scholarship at Harvard (DASH) (Harvard University)
- Authors
- Pace, M. J., Graf, E. H., & O'Doherty, U.
- Affiliations
- University of Pennsylvania (US)
- Venue
- Virology
- Publisher
- Elsevier BV
- Published
- 2013-06
- Volume
- 441
- Issue
- 1
- Pages
- 18-21
- ISSN
- 0042-6822 (ISSN-L)
- PMC
- PMC3983779
- OpenAlex
- W2023756765
- Cited by
- 34
- References
- 26
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 6 · 2017: 4 · 2016: 9 · 2015: 4 · 2014: 3 · 2013: 1
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Virology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Pennsylvania
- U.S. Public Health Service (R21A1087461)
- National Institute of Allergy and Infectious Diseases (R21AI096993, R21AI087461)
- 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
- HIV reservoir, CD4+ T cells, integrated HIV DNA, TREC, HIV cure, primary T cells
- MeSH terms
- Cells, Cultured, DNA, Circular, DNA, Viral, Humans, Time Factors, CD4-Positive T-Lymphocytes, HIV-2, HIV Long Terminal Repeat, Genomic Instability
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