ReviewThe Journal of infectious diseases2021
Low Inducibility of Latent Human Immunodeficiency Virus Type 1 Proviruses as a Major Barrier to Cure.
Review in The Journal of infectious diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
- HIV superinfection reveals sequential reservoir reactivation and immune-driven rebound dynamics.Journal of virology · 2026Article
- The rebound-initiating viral reservoir (RIVR) in SIV/SHIV infection is dominated by plasma virus sequences present at the time of ART initiation.Journal of virology · 2026Article
- 5' leader defects drive persistent HIV-1 viremia on long-term ART.Nature communications · 2026Article
- Histone decrotonylation plays a distinct role in HIV latency.Science advances · 2026Article
- HIV-2 infection as a comparative lens for functional HIV-1 remission.Frontiers in immunology · 2026Review
- Enhanced HIV-1 Control After Antibody Therapy is Associated with Autologous Antibodies and Reservoir Clearance in the RIO trial.medRxiv : the preprint server for health sciences · 2025Article
- Proviruses in CD4Science translational medicine · 2025Article
- Applications and limitations of the passenger hypothesis for HIV reservoir persistence and cure.Journal of virology · 2025Review
- Immune-mediated strategies to solving the HIV reservoir problem.Nature reviews. Immunology · 2025Review
- CBP/p300 lysine acetyltransferases inhibit HIV-1 expression in latently infected T cells.iScience · 2024Article
- Article
- Specific quantification of inducible HIV-1 reservoir by RT-LAMP.Communications medicine · 2024Article
- CD20 CAR T cells safely and reversibly ablate B cell follicles in a non-human primate model of HIV persistence.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- The cell biology of HIV-1 latency and rebound.Retrovirology · 2024Review
- A novel high-throughput microwell outgrowth assay for HIV-infected cells.Journal of virology · 2024Article
- Small molecule inhibitors of transcriptional cyclin-dependent kinases impose HIV-1 latency, presenting "block and lock" treatment strategies.Antimicrobial agents and chemotherapy · 2024Article
- TGF-β blockade drives a transitional effector phenotype in T cells reversing SIV latency and decreasing SIV reservoirs in vivo.Nature communications · 2024Article
- Preservation of functionality, immunophenotype, and recovery of HIV RNA from PBMCs cryopreserved for more than 20 years.Frontiers in immunology · 2024Article
- A histone deacetylase network regulates epigenetic reprogramming and viral silencing in HIV-infected cells.Cell chemical biology · 2023Article
- Controversies in the Design of Strategies for the Cure of HIV Infection.Pathogens (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
The latent reservoir for human immunodeficiency virus type 1 (HIV-1) in resting CD4+ T cells is a major barrier to cure. The dimensions of the reservoir problem can be defined with 2 assays. A definitive minimal estimate of the frequency of latently infected cells is provided by the quantitative viral outgrowth assay (QVOA), which detects cells that can be induced by T-cell activation to release infectious virus. In contrast, the intact proviral DNA assay (IPDA) detects all genetically intact proviruses and provides a more accurate upper limit on reservoir size than standard single-amplicon polymerase chain reaction assays which mainly detect defective proviruses. The frequency of cells capable of initiating viral rebound on interruption of antiretroviral therapy lies between the values produced by the QVOA and the IPDA. We argue here that the 1-2-log difference between QVOA and IPDA values in part reflects that the fact that many replication-competent proviruses are not readily induced by T-cell activation. Findings of earlier studies suggest that latently infected cells can be activated to proliferate in vivo without expressing viral genes. The proliferating cells nevertheless retain the ability to produce virus on subsequent stimulation. The low inducibility of latent proviruses is a major problem for the shock-and-kill strategy for curing HIV-1 infection, which uses latency-reversing agents to induce viral gene expression and render infected cells susceptible to immune clearance. The latency-reversing agents developed to date are much less effective at reversing latency than T-cell activation. Taken together, these results indicate that HIV-1 eradication will require the discovery of much more effective ways to induce viral gene expression.
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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.