ArticleJCI insight2018
Dual TLR2 and TLR7 agonists as HIV latency-reversing agents.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
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The trial behind it
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Who cites it
55 citing papers in PubMed, 77 citations in OpenAlex.
- Transcriptomic Signatures of Immune Suppression and Cellular Dysfunction Distinguish Latent from Transcriptionally Active HIV-1 Infection in Dendritic Cells.International journal of molecular sciences · 2026Article
- Host-directed approaches in the pursuit of a cure for HIV.Antiviral research · 2025Review
- Biological sex and age influence GS-9620 activity ex vivo.JCI insight · 2025Article
- Latency Reversing Agents and the Road to an HIV CurePathogens (Basel, Switzerland) · 2025Review
- The impact of sex on HIV immunopathogenesis and therapeutic interventions.The Journal of clinical investigation · 2024Review
- Noncanonical-NF-κB activation and DDX3 inhibition reduces the HIV-1 reservoir by elimination of latently infected cellsMicrobiology spectrum · 2024Article
- Association of Toll-Like Receptor Gene Polymorphisms with Tuberculosis in HIV-Positive Participants.Epigenomes · 2023Article
- Identification of aryl hydrocarbon receptor as a barrier to HIV-1 infection and outgrowth in CD4Cell reports · 2023Article
- TLR7 Agonist GS-9620 Combined with Nicotinamide Generate Viral Reactivation in Seronegative SHIVBiomedicines · 2023Article
- Toll-like Receptor Response to Human Immunodeficiency Virus Type 1 or Co-Infection with Hepatitis B or C Virus: An Overview.International journal of molecular sciences · 2023Review
- Therapeutic immunomodulation by rationally designed nucleic acids and nucleic acid nanoparticles.Frontiers in immunology · 2023Review
- Strategies for HIV-1 suppression through key genes and cell therapy.Frontiers in medicine · 2023Review
- Novel TLR7/8 agonists promote activation of HIV-1 latent reservoirs and human T and NK cells.Frontiers in microbiology · 2023Article
- PolyIC-coated Prussian blue nanoparticles as a dual-mode HIV latency reversing agent.Nanomedicine (London, England) · 2022Article
- Toll-like Receptor Mediation in SARS-CoV-2: A Therapeutic Approach.International journal of molecular sciences · 2022Review
- SARS CoV-2 mRNA vaccination exposes latent HIV to Nef-specific CD8Nature communications · 2022Article
- Unraveling the Tomaralimab Epitope on the Toll-like Receptor 2 via Molecular Dynamics and Deep Learning.ACS omega · 2022Article
- HIV cure strategies: which ones are appropriate for Africa?Cellular and molecular life sciences : CMLS · 2022Review
- Changes to the Simian Immunodeficiency Virus (SIV) Reservoir and Enhanced SIV-Specific Responses in a Rhesus Macaque Model of Functional Cure after Serial Rounds of Romidepsin Administrations.Journal of virology · 2022Article
- So Pathogenic or So What?-A Brief Overview of SIV Pathogenesis with an Emphasis on Cure Research.Viruses · 2022Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
The presence of a reservoir of latently infected cells in HIV-infected patients is a major barrier towards finding a cure. One active cure strategy is to find latency-reversing agents that induce viral reactivation, thus leading to immune cell recognition and elimination of latently infected cells, known as the shock-and-kill strategy. Therefore, the identification of molecules that reactivate latent HIV and increase immune activation has the potential to further these strategies into the clinic. Here, we characterized synthetic molecules composed of a TLR2 and a TLR7 agonist (dual TLR2/7 agonists) as latency-reversing agents and compared their activity with that of the TLR2 agonist Pam2CSK4 and the TLR7 agonist GS-9620. We found that these dual TLR2/7 agonists reactivate latency by 2 complementary mechanisms. The TLR2 component reactivates HIV by inducing NF-κB activation in memory CD4+ T cells, while the TLR7 component induces the secretion of TNF-α by monocytes and plasmacytoid dendritic cells, promoting viral reactivation in CD4+ T cells. Furthermore, the TLR2 component induces the secretion of IL-22, which promotes an antiviral state and blocks HIV infection in CD4+ T cells. Our study provides insight into the use of these agonists as a multipronged approach targeting eradication of latent HIV.
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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.