ArticleFrontiers in microbiology2023
Novel TLR7/8 agonists promote activation of HIV-1 latent reservoirs and human T and NK cells.
Article in Frontiers in microbiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- A tissue-intrinsic mechanism sensitizes HIV-1 particles for TLR-triggered innate immune responses.Nature communications · 2026Article
- Sex-Specific Factors Influencing HIV Infection.Immunological reviews · 2026Review
- T cell-intrinsic PRR signaling in immunity and pathology.Acta biochimica et biophysica Sinica · 2026Review
- SARS-CoV-2-Induced Macrophage Polarization Reverses HIV-1 Latency in J-Lat Cells Through TNFα Signaling.Journal of immunology research · 2026Article
- Challenges in the Vaccination of HIV-Infected Individuals.Vaccines · 2025Review
- Grand Challenges on HIV/AIDS in China - The 5th Symposium, Yunnan 2024.Emerging microbes & infections · 2025Article
- HIV and the gut: implications for HIV persistence, immune dysfunction and cure strategies.Frontiers in immunology · 2025Review
- AI discovery of TLR agonist-driven phenotypes reveals unique features of peripheral cells from healthy donors and ART-suppressed people living with HIV.Frontiers in immunology · 2025Article
- Article
- Inhibitory receptor CD47 binding to plasma TSP1 suppresses NK-cell IFN-γ production via activating the JAK/STAT3 pathway during HIV infection.Journal of translational medicine · 2023Article
- Lymph node dendritic cells harbor inducible replication-competent HIV despite years of suppressive ART.Cell host & microbe · 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
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Authors and funding
10 authors.
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Abstract
Antiretroviral therapy can successfully suppress HIV-1 replication to undetectable levels but fails to eliminate latent and persistent HIV-1 reservoirs. Recent studies have focused on the immunomodulatory agents such as Toll-like receptor 7 and 8 (TLR7 and TLR8) capable of activating, thereby rendering the reservoir susceptible to antiretroviral inhibition and immune recognition and elimination. In this context, this study focused on generating a diverse repertoire of TLR7/8 agonists to identify more potent candidates for activating latent HIV-1 and immune cells' response. Through combinational strategies of computer-aided design and biological characterization, 159 pyrido [3,2-d] pyrimidine and pyridine-2-amine-based derivatives were synthesized. Of which, two TLR7/8 dual and one TLR8-specific agonists with exceptionally high potency in activating HIV-1 latent reservoirs in cell lines and PBMCs of patients with persistent and durable virologic controls were identified. Particularly, these agonists appeared to enhance NK and T cells activity, which were correlated with the degree of surface activation markers. The outcome of this study highlights the remarkable potential of TLR7/8 agonists in simultaneously activating HIV-1 from the latently infected cells and augmenting immune effector cells.
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