HIV reproducibly establishes a latent infection after acute infection of T cells in vitro
Open accessAbstract
The presence of latent reservoirs has prevented the eradication of human immunodeficiency virus (HIV) from infected patients successfully treated with anti-retroviral therapy. The mechanism of postintegration latency is poorly understood, partly because of the lack of an in vitro model. We have used an HIV retroviral vector or a full-length HIV genome expressing green fluorescent protein to infect a T lymphocyte cell line in vitro and highly enrich for latently infected cells. HIV latency occurred reproducibly, albeit with low frequency, during an acute infection. Clonal cell lines derived from latent populations showed no detectable basal expression, but could be transcriptionally activated after treatment with phorbol esters or tumor necrosis factor alpha. Direct sequencing of integration sites demonstrated that latent clones frequently contain HIV integrated in or close to alphoid repeat elements in heterochromatin. This is in contrast to a productive infection where integration in or near heterochromatin is disfavored. These observations demonstrate that HIV can reproducibly establish a latent infection as a consequence of integration in or near heterochromatin.
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Ablation of HIV-1 genome by Cas9/LTR-A/B gRNAs was validated in latently infected J-Lat T cells harboring integrated HIV-R7/E-/EGFP using flow cytometry analysis, SURVEYOR assay, and PCR genotyping.
“We also validated the ablation of HIV-1 genome by Cas9/ LTR-A/B gRNAs in latently infected J-Lat T cells harboring integrated HIV-R7/E-/EGFP (21) using flow cytometry analysis, SURVEYOR assay, and PCR genotyping”
From RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection (2014) · cites this paper as [21]
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- Authors
- Jordan, A., Bisgrove, D., & Verdin, E.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Verdin, Eric
- Venue
- The EMBO Journal
- Published
- 2003-04-15
- Volume
- 22
- Issue
- 8
- Pages
- 1868-1877
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC154479
- OpenAlex
- W2063628696
- Cited by
- 914
- References
- 34
- Citations by year
- 2026: 34 · 2025: 57 · 2024: 53 · 2023: 55 · 2022: 62 · 2021: 54 · 2020: 62 · 2019: 46 · 2018: 53 · 2017: 53 · 2016: 41 · 2015: 48 · 2014: 32 · 2013: 39 · 2012: 36
- FWCI
- 5.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Gladstone Institutes
- Fondation pour la Recherche Médicale
- National Institutes of Health
- National Institute of General Medical Sciences (GM51671-05A2, R01GM051671)
- 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 latency, latent reservoir, T cell infection, HIV integration sites, heterochromatin, transcriptional activation, phorbol ester, TNF-α, HIV reactivation, in vitro infection model
- MeSH terms
- Cell Line, Cell Separation, Flow Cytometry, Humans, Luminescent Proteins, Promoter Regions, Genetic, T-Lymphocytes, Transcription, Genetic, Virus Activation, HIV-1, HIV Infections, Gene Expression Regulation, Viral, Virus Integration, Virus Latency, Jurkat Cells, Green Fluorescent Proteins
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