ArticlePLoS pathogens2017
Ex vivo activation of CD4+ T-cells from donors on suppressive ART can lead to sustained production of infectious HIV-1 from a subset of infected cells.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 46 citations in OpenAlex.
- Article
- Transcription of HIV-1 is heterogenous among authentic latent CD4+ T cell clones.The Journal of experimental medicine · 2026Article
- Identification of inducible HIV reservoirs in tonsillar, intestinal and cervical tissue models of HIV latency.Nature communications · 2025Article
- Latency Reversing Agents and the Road to an HIV CurePathogens (Basel, Switzerland) · 2025Review
- Single-Cell Transcriptomics ofCells · 2023Review
- Genotypic and Phenotypic Diversity of the Replication-Competent HIV Reservoir in Treated Patients.Microbiology spectrum · 2022Article
- Liposomal phytohemagglutinin: In vivo T-cell activator as a novel pan-cancer immunotherapy.Journal of cellular and molecular medicine · 2022Article
- Review
- Article
- Biogenesis of P-TEFb in CD4+ T cells to reverse HIV latency is mediated by protein kinase C (PKC)-independent signaling pathways.PLoS pathogens · 2021Article
- Computational Design of gRNAs Targeting Genetic Variants Across HIV-1 Subtypes for CRISPR-Mediated Antiviral Therapy.Frontiers in cellular and infection microbiology · 2021Article
- The Correlation Between Platelet-to-Lymphocyte Ratio and Neutrophil-to-Lymphocyte Ratio with Hepatic Echinococcosis.Journal of inflammation research · 2021Article
- Nonsuppressible HIV-1 viremia: a reflection of how the reservoir persists.The Journal of clinical investigation · 2020Article
- HIV-1 viremia not suppressible by antiretroviral therapy can originate from large T cell clones producing infectious virus.The Journal of clinical investigation · 2020Article
- HIV infects astrocytes in vivo and egresses from the brain to the periphery.PLoS pathogens · 2020Article
- Combination Immune Checkpoint Blockade to Reverse HIV Latency.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Advances in Developing CAR T-Cell Therapy for HIV Cure.Frontiers in immunology · 2020Review
- Combined HIV-1 sequence and integration site analysis informs viral dynamics and allows reconstruction of replicating viral ancestors.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- HIV Rebound Is Predominantly Fueled by Genetically Identical Viral Expansions from Diverse Reservoirs.Cell host & microbe · 2019Article
- Review: HIV-1 phylogeny during suppressive antiretroviral therapy.Current opinion in HIV and AIDS · 2019Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
The fate of HIV-infected cells after reversal of proviral latency is not well characterized. Simonetti, et al. recently showed that CD4+ T-cells containing intact proviruses can clonally expand in vivo and produce low-level infectious viremia. We hypothesized that reversal of HIV latency by activation of CD4+ T-cells can lead to the expansion of a subset of virus-producing cells rather than their elimination. We established an ex vivo cell culture system involving stimulation of CD4+ T-cells from donors on suppressive antiretroviral therapy (ART) with PMA/ionomycin (day 1-7), followed by rest (day 7-21), and then repeat stimulation (day 21-28), always in the presence of high concentrations of raltegravir and efavirenz to effectively block new cycles of viral replication. HIV DNA and virion RNA in the supernatant were quantified by qPCR. Single genome sequencing (SGS) of p6-PR-RT was performed to genetically characterize proviruses and virion-associated genomic RNA. The replication-competence of the virions produced was determined by the viral outgrowth assay (VOA) and SGS of co-culture supernatants from multiple time points. Experiments were performed with purified CD4+ T-cells from five consecutively recruited donors who had been on suppressive ART for > 2 years. In all experiments, HIV RNA levels in supernatant increased following initial stimulation, decreased or remained stable during the rest period, and increased again with repeat stimulation. HIV DNA levels did not show a consistent pattern of change. SGS of proviruses revealed diverse outcomes of infected cell populations, ranging from their apparent elimination to persistence and expansion. Importantly, a subset of infected cells expanded and produced infectious virus continuously after stimulation. These findings underscore the complexity of eliminating reservoirs of HIV-infected cells and highlight the need for new strategies to kill HIV-infected cells before they can proliferate.
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