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Single-cell analysis of HIV-1 transcriptional activity reveals expression of proviruses in expanded clones during ART
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Significance: Previously, we showed that the virus that persists in human immunodeficiency virus (HIV)-infected individuals on antiretroviral therapy (ART) is derived from cells infected prior to initiating treatment. We also showed that HIV-infected cells can undergo cellular proliferation during ART. However, it is not known what fraction of infected cells that persist during ART are latent and what fraction are actively producing HIV RNA. The method described here was developed to determine the fraction of infected cells that produce HIV RNA and the levels of HIV RNA in single cells, including cells that have undergone cellular proliferation. Additionally, the method can be used to identify the sources of rebound virus after stopping ART and the efficacy of experimental interventions designed to cure HIV infection.
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“Conversely, a multitude of studies showed that defective HIV-1 genomes inside cells may still produce individual viral transcripts or proteins, 33-35,55 which could be mistaken as indicators of a functional reservoir of infectious virus.”
From Revealing viral and cellular dynamics of HIV-1 at the single-cell level during early treatment periods (2023) · cites this paper as [55]
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Metadata
- Authors
- Wiegand, A., Spindler, J., Hong, F. F., Shao, W., Cyktor, J. C., Cillo, A. R., Halvas, E. K., Coffin, J. M., Mellors, J. W., & Kearney, M. F.
- Affiliations
- National Cancer Institute (US)
- University of Pittsburgh (US)
- Frederick National Laboratory for Cancer Research (US)
- Tufts University (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-04-17
- Volume
- 114
- Issue
- 18
- Pages
- E3659-E3668
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5422779
- OpenAlex
- W2606857030
- Cited by
- 165
- References
- 44
- Citations by year
- 2026: 8 · 2025: 19 · 2024: 15 · 2023: 17 · 2022: 15 · 2021: 19 · 2020: 25 · 2019: 19 · 2018: 23 · 2017: 4
- FWCI
- 10.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Cancer Institute (Intramural Funding, 1U01CA200441)
- 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-1, unspliced viral RNA, single-genome sequencing, antiretroviral therapy, viral reservoir, defective proviruses, HIV transcription, viremia, blood mononuclear cells
- MeSH terms
- Female, Humans, Leukocytes, Mononuclear, Male, Proviruses, RNA, Viral, Transcription, Genetic, HIV-1, Gene Expression Regulation, Viral, Anti-Retroviral Agents
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