ArticleJournal of virology2015
A Subset of CD4/CD8 Double-Negative T Cells Expresses HIV Proteins in Patients on Antiretroviral Therapy.
Article in Journal of virology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
55 citing papers in PubMed, 65 citations in OpenAlex.
- Standard vaccines increase HIV-1 transcription during antiretroviral therapy.AIDS (London, England) · 2016Trial
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- The TLR7 agonist vesatolimod does not measurably induce SIV expression in macaques receiving combination antiretroviral therapy initiated during chronic infection.Antimicrobial agents and chemotherapy · 2025Article
- Role of HIV-encoded proteins in cardiovascular disease.American journal of physiology. Cell physiology · 2025Review
- A Lymphocyte Subset-Based Prediction Model for Refractory Community-Acquired Pneumonia in Immunocompetent Patients.Diagnostics (Basel, Switzerland) · 2025Article
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- Inhibition of TIGIT on NK cells improves their cytotoxicity and HIV reservoir eradication potential.mBio · 2025Article
- Nuclear retention of unspliced HIV-1 RNA as a reversible post-transcriptional block in latency.Nature communications · 2025Article
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- The latency-reversing agent HODHBt synergizes with IL-15 to enhance cytotoxic function of HIV-specific T cells.JCI insight · 2023Article
- HIV associated cell death: Peptide-induced apoptosis restricts viral transmission.Frontiers in immunology · 2023Article
- Frequency and functional profile of circulating TCRαβBMC infectious diseases · 2022Article
- Immune mobilising T cell receptors redirect polyclonal CD8Scientific reports · 2022Article
- Double-negative T cells are increased in HIV-infected patients under antiretroviral therapy.Medicine · 2022Article
- Investigating vascular diseases in people living with HIV by nuclear imaging.Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology · 2022Article
- HIV Compartmentalization in the CNS and Its Impact in Treatment Outcomes and Cure Strategies.Current HIV/AIDS reports · 2022Review
- The HIV-1 proviral landscape reveals that Nef contributes to HIV-1 persistence in effector memory CD4+ T cells.The Journal of clinical investigation · 2022Article
- Mega-High-Throughput Screening Platform for the Discovery of Biologically Relevant Sequence-Defined Non-Natural Polymers.ACS central science · 2022Article
- CD3Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
unlabelledA major goal in HIV eradication research is characterizing the reservoir cells that harbor HIV in the presence of antiretroviral therapy (ART), which reseed viremia after treatment is stopped. In general, it is assumed that the reservoir consists of CD4(+) T cells that express no viral proteins. However, recent findings suggest that this may be an overly simplistic view and that the cells that contribute to the reservoir may be a diverse population that includes both CD4(+) and CD4(-) cells. In this study, we directly infected resting CD4(+) T cells and used fluorescence-activated cell sorting (FACS) and fiber-optic array scanning technology (FAST) to identify and image cells expressing HIV Gag. We found that Gag expression from integrated proviruses occurred in resting cells that lacked surface CD4, likely resulting from Nef- and Env-mediated receptor internalization. We also extended our approach to detect cells expressing HIV proteins in patients suppressed on ART. We found evidence that rare Gag(+) cells persist during ART and that these cells are often negative for CD4. We propose that these double-negative α/β T cells that express HIV protein may be a component of the long-lived reservoir. IMPORTANCE: A reservoir of infected cells persists in HIV-infected patients during antiretroviral therapy (ART) that leads to rebound of virus if treatment is stopped. In this study, we used flow cytometry and cell imaging to characterize protein expression in HIV-infected resting cells. HIV Gag protein can be directly detected in infected resting cells and occurs with simultaneous loss of CD4, consistent with the expression of additional viral proteins, such as Env and Nef. Gag(+) CD4(-) cells can also be detected in suppressed patients, suggesting that a subset of infected cells express proteins during ART. Understanding the regulation of viral protein expression during ART will be key to designing effective strategies to eradicate HIV reservoirs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.