Cited by 166HIV Research and TreatmentVirus-based gene therapy researchHIV/AIDS drug development and treatment

Single-cell analysis of HIV-1 transcriptional activity reveals expression of proviruses in expanded clones during ART

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Wiegand, Ann, Spindler, Jonathan, Hong, Feiyu F., Shao, Wei, Cyktor, Joshua C., Cillo, Anthony R., Halvas, Elias K., Coffin, John M. +2 more·2017·Proceedings of the National Academy of Sciences

Abstract

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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  • A multitude of studies showed that defective HIV-1 genomes inside cells may still produce individual viral transcripts or proteins, which could be mistaken as indicators of a functional reservoir of infectious virus.

    “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.”

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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)
Venue
Proceedings of the National Academy of Sciences
Published
2017-04-17
Volume
114
Issue
18
Pages
E3659-E3668
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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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