ArticleRetrovirology2013
Reactivation of latent HIV-1 in central memory CD4⁺ T cells through TLR-1/2 stimulation.
Article in Retrovirology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 129 citations in OpenAlex.
- 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
- Evaluation of the immunogenicity and impact on the latent HIV-1 reservoir of a conserved region vaccine, MVA.HIVconsv, in antiretroviral therapy-treated subjects.Journal of the International AIDS Society · 2017Trial
- PKC inhibitors reveal PKC isoforms involved in HIV latency reversal and immunomodulation.Journal of virology · 2026Article
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- Host-directed approaches in the pursuit of a cure for HIV.Antiviral research · 2025Review
- Latency Reversing Agents and the Road to an HIV CurePathogens (Basel, Switzerland) · 2025Review
- HIV and the gut: implications for HIV persistence, immune dysfunction and cure strategies.Frontiers in immunology · 2025Review
- Enhancing broadly neutralising antibody suppression of HIV by immune modulation and vaccination.Frontiers in immunology · 2024Review
- Viral Persistence in the Gut-Associated Lymphoid Tissue and Barriers to HIV Cure.AIDS research and human retroviruses · 2023Article
- Multimeric immunotherapeutic complexes activating natural killer cells towards HIV-1 cure.Journal of translational medicine · 2023Article
- Association of Toll-Like Receptor Gene Polymorphisms with Tuberculosis in HIV-Positive Participants.Epigenomes · 2023Article
- Trispecific antibody targeting HIV-1 and T cells activates and eliminates latently-infected cells in HIV/SHIV infections.Nature communications · 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
- Pharmacological Inhibition of IKK to Tackle Latency and Hyperinflammation in Chronic HIV-1 Infection.International journal of molecular sciences · 2022Article
- Review
- SARS CoV-2 mRNA vaccination exposes latent HIV to Nef-specific CD8Nature communications · 2022Article
- Engaging innate immunity in HIV-1 cure strategies.Nature reviews. Immunology · 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
- The ingenol-based protein kinase C agonist GSK445A is a potent inducer of HIV and SIV RNA transcription.PLoS pathogens · 2022Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundToll-like receptors (TLRs) are crucial for recognition of pathogen-associated molecular patterns by cells of the innate immune system. TLRs are present and functional in CD4⁺ T cells. Memory CD4⁺ T cells, predominantly central memory cells (TCM), constitute the main reservoir of latent HIV-1. However, how TLR ligands affect the quiescence of latent HIV within central memory CD4⁺ T cells has not been studied.
resultsWe evaluated the ability of a broad panel of TLR agonists to reactivate latent HIV-1. The TLR-1/2 agonist Pam3CSK4 leads to viral reactivation of quiescent HIV in a model of latency based on cultured TCM and in resting CD4⁺ T cells isolated from aviremic patients. In addition, we investigated the signaling pathway associated with Pam3CSK4 involved in HIV-1 reactivation. We show that the transcription factors NFκB, NFAT and AP-1 cooperate to induce viral reactivation downstream of TLR-1/2 stimulation. Furthermore, increasing levels of cyclin T1 is not required for TLR-mediated viral reactivation, but induction of viral expression requires activated pTEFb. Finally, Pam3CSK4 reactivates latent HIV-1 in the absence of T cell activation or proliferation, in contrast to antigen stimulation.
conclusionsOur findings suggest that the signaling through TLR-1/2 pathway via Pam3CSK4 or other reagents should be explored as an anti-latency strategy either alone or in combination with other anti-latency drugs.
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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.