ArticleJCI insight2022
Blockade of TGF-β signaling reactivates HIV-1/SIV reservoirs and immune responses in vivo.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
19 citing papers in PubMed, 22 citations in OpenAlex.
- 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
- A Tissue Virus Microenvironment with Activated Stress Responses Underlies Durable SIV Persistence.bioRxiv : the preprint server for biology · 2026Article
- HIV-seq reveals gene expression differences between HIV-transcribing cells from viremic and suppressed people with HIV.Nature communications · 2026Article
- Single-cell capture of on-ART SIV transcription reveals TGF-β-mediated metabolic control of viral latency.JCI insight · 2026Article
- A tissue microenvironment analogous to certain tumor microenvironments facilitates HIV persistence.Frontiers in immunology · 2026Article
- Whole-body PET imaging of simian immunodeficiency virus using gp120-targeting probes fails to reveal regions of specific uptake in rhesus macaques.European journal of nuclear medicine and molecular imaging · 2025Article
- Immune Alterations and Viral Reservoir Atlas in SIV-Infected Chinese Rhesus Macaques.Infectious disease reports · 2025Review
- Neuroinflammation associated with proviral DNA persists in the brain of virally suppressed people with HIV.Frontiers in immunology · 2025Article
- The spatial biology of HIV infection.PLoS pathogens · 2025Review
- Double, double toil and trouble: transforming growth factor beta (TGF-β) in HIV infection.Frontiers in immunology · 2025Review
- Footprints of innate immune activity during HIV-1 reservoir cell evolution in early-treated infection.The Journal of experimental medicine · 2024Article
- The immunosuppressive tuberculosis-associated microenvironment inhibits viral replication and promotes HIV-1 latency in CD4iScience · 2024Article
- TGF-β blockade drives a transitional effector phenotype in T cells reversing SIV latency and decreasing SIV reservoirs in vivo.Nature communications · 2024Article
- Polymorphonuclear myeloid-derived suppressor cells regulates immune recovery during HIV infection through PD-L1 and TGF-β pathways.Frontiers in cellular and infection microbiology · 2024Article
- Breaking the Silence: Regulation of HIV Transcription and Latency on the Road to a Cure.Viruses · 2023Review
- Review
- Article
- NK cell subsets and dysfunction during viral infection: a new avenue for therapeutics?Frontiers in immunology · 2023Review
- The role of CD101-expressing CD4 T cells in HIV/SIV pathogenesis and persistence.PLoS pathogens · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
25 authors at 5 institutions in 1 country.
Funding
Abstract
TGF-β plays a critical role in maintaining immune cells in a resting state by inhibiting cell activation and proliferation. Resting HIV-1 target cells represent the main cellular reservoir after long-term antiretroviral therapy (ART). We hypothesized that releasing cells from TGF-β-driven signaling would promote latency reversal. To test our hypothesis, we compared HIV-1 latency models with and without TGF-β and a TGF-β type 1 receptor inhibitor, galunisertib. We tested the effect of galunisertib in SIV-infected, ART-treated macaques by monitoring SIV-env expression via PET/CT using the 64Cu-DOTA-F(ab')2 p7D3 probe, along with plasma and tissue viral loads (VLs). Exogenous TGF-β reduced HIV-1 reactivation in U1 and ACH-2 models. Galunisertib increased HIV-1 latency reversal ex vivo and in PBMCs from HIV-1-infected, ART-treated, aviremic donors. In vivo, oral galunisertib promoted increased total standardized uptake values in PET/CT images in gut and lymph nodes of 5 out of 7 aviremic, long-term ART-treated, SIV-infected macaques. This increase correlated with an increase in SIV RNA in the gut. Two of the 7 animals also exhibited increases in plasma VLs. Higher anti-SIV T cell responses and antibody titers were detected after galunisertib treatment. In summary, our data suggest that blocking TGF-β signaling simultaneously increases retroviral reactivation events and enhances anti-SIV immune responses.
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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.