ArticlePLoS pathogens2016
A Subset of Latency-Reversing Agents Expose HIV-Infected Resting CD4+ T-Cells to Recognition by Cytotoxic T-Lymphocytes.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.
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Who cites it
126 citing papers in PubMed.
- Poly-ICLC, a TLR3 Agonist, Induces Transient Innate Immune Responses in Patients With Treated HIV-Infection: A Randomized Double-Blinded Placebo Controlled Trial.Frontiers in immunology · 2019Trial
- Enhancing HIV-1-specific CAR-T cell functional activity by treatment with a novel cytokine-based scaffold with IL-15 superagonist and TGF-β-neutralizing activity.Journal of virology · 2026Article
- Recent advances in molecular mechanisms to improve the efficacy of CAR-T cell therapy for viral diseases, cancer, and autoimmune diseases.Stem cell research & therapy · 2026Review
- Granulocytic myeloid-derived suppressor cells sustain HIV reservoirs by inhibiting viral reactivation via arginase 1-mediated mechanisms.JCI insight · 2026Article
- PKC inhibitors reveal PKC isoforms involved in HIV latency reversal and immunomodulation.Journal of virology · 2026Article
- Breaking into HIV-1's Epigenetic Vault: Cure Strategies to Eliminate the Viral Reservoir.Viruses · 2026Review
- IL-7/IL-15/IL-21 cytokine-fusion scaffold generates highly functional CAR T cells enriched in long-lived T memory stem cells.Science advances · 2026Article
- Retinoids enhance NK effector function against HIV-infected CD4 T cells.Journal of virology · 2026Article
- Viral Vertical Transmission through the Placenta: The Potential of Natural Products as Therapeutic and Prophylactic Antiviral Agents.Current topics in medicinal chemistry · 2026Review
- Identification of inducible HIV reservoirs in tonsillar, intestinal and cervical tissue models of HIV latency.Nature communications · 2025Article
- Balancing Host Defense and Viral Tolerance for the Development of Next-Generation Broad-Spectrum Antiviral Agents.Pathogens (Basel, Switzerland) · 2025Review
- Host-directed approaches in the pursuit of a cure for HIV.Antiviral research · 2025Review
- Impact of the IL-15 superagonist N-803 on lymphatic reservoirs of HIV.JCI insight · 2025Article
- EZH2 inhibition mitigates HIV immune evasion, reduces reservoir formation, and promotes skewing of CD8Cell reports · 2025Article
- Latency Reversing Agents and the Road to an HIV CurePathogens (Basel, Switzerland) · 2025Review
- From natural defenders to therapeutic warriors: NK cells in HIV immunotherapy.Immunotherapy · 2025Review
- SIV Env RhmAbs + N-803 at ART initiation prolongs viral decay without disrupting reservoir establishment in SIV-infected infant macaques.PLoS pathogens · 2025Article
- The Proviral Reservoirs of Human Immunodeficiency Virus (HIV) Infection.Pathogens (Basel, Switzerland) · 2024Review
- Footprints of innate immune activity during HIV-1 reservoir cell evolution in early-treated infection.The Journal of experimental medicine · 2024Article
- Isotretinoin promotes elimination of translation-competent HIV latent reservoirs in CD4T cells.PLoS pathogens · 2024Article
66 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
26 authors.
Funding
Abstract
Resting CD4+ T-cells harboring inducible HIV proviruses are a critical reservoir in antiretroviral therapy (ART)-treated subjects. These cells express little to no viral protein, and thus neither die by viral cytopathic effects, nor are efficiently cleared by immune effectors. Elimination of this reservoir is theoretically possible by combining latency-reversing agents (LRAs) with immune effectors, such as CD8+ T-cells. However, the relative efficacy of different LRAs in sensitizing latently-infected cells for recognition by HIV-specific CD8+ T-cells has not been determined. To address this, we developed an assay that utilizes HIV-specific CD8+ T-cell clones as biosensors for HIV antigen expression. By testing multiple CD8+ T-cell clones against a primary cell model of HIV latency, we identified several single agents that primed latently-infected cells for CD8+ T-cell recognition, including IL-2, IL-15, two IL-15 superagonists (IL-15SA and ALT-803), prostratin, and the TLR-2 ligand Pam3CSK4. In contrast, we did not observe CD8+ T-cell recognition of target cells following treatment with histone deacetylase inhibitors or with hexamethylene bisacetamide (HMBA). In further experiments we demonstrate that a clinically achievable concentration of the IL-15 superagonist 'ALT-803', an agent presently in clinical trials for solid and hematological tumors, primes the natural ex vivo reservoir for CD8+ T-cell recognition. Thus, our results establish a novel experimental approach for comparative evaluation of LRAs, and highlight ALT-803 as an LRA with the potential to synergize with CD8+ T-cells in HIV eradication strategies.
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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.