ArticlePLoS pathogens2019
Reiterative Enrichment and Authentication of CRISPRi Targets (REACT) identifies the proteasome as a key contributor to HIV-1 latency.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 53 citations in OpenAlex.
- New hope and promise with CRISPR-Cas9 technology for the treatment of HIV.Functional & integrative genomics · 2025Review
- Interleukin-27-polarized HIV-resistant M2 macrophages are a novel subtype of macrophages that express distinct antiviral gene profiles in individual cells: implication for the antiviral effect via different mechanisms in the individual cell-dependent manner.Frontiers in immunology · 2025Article
- An HIV-1 CRISPR-Cas9 membrane trafficking screen reveals a role for PICALM intersecting endolysosomes and immunity.iScience · 2024Article
- The cell biology of HIV-1 latency and rebound.Retrovirology · 2024Review
- Ectopic USP15 expression inhibits HIV-1 transcription involving changes in YY1 deubiquitination and stability.Frontiers in cellular and infection microbiology · 2024Article
- Dynamic modulation of the non-canonical NF-κB signaling pathway for HIV shock and kill.Frontiers in cellular and infection microbiology · 2024Review
- PRMT2 promotes HIV-1 latency by preventing nucleolar exit and phase separation of Tat into the Super Elongation Complex.Nature communications · 2023Article
- Comprehensive synergy mapping links a BAF- and NSL-containing "supercomplex" to the transcriptional silencing of HIV-1.Cell reports · 2023Article
- Identification of Human Host Substrates of the SARS-CoV-2 MACS infectious diseases · 2023Article
- A modular CRISPR screen identifies individual and combination pathways contributing to HIV-1 latency.PLoS pathogens · 2023Article
- Article
- Medicinal Chemistry of Anti-HIV-1 Latency Chemotherapeutics: Biotargets, Binding Modes and Structure-Activity Relationship Investigation.Molecules (Basel, Switzerland) · 2022Review
- Genome-wide CRISPR screens identify combinations of candidate latency reversing agents for targeting the latent HIV-1 reservoir.Science translational medicine · 2022Article
- Application of CRISPR-Cas9 Gene Editing for HIV Host Factor Discovery and Validation.Pathogens (Basel, Switzerland) · 2022Review
- PARP1 Might Substitute HSF1 to Reactivate Latent HIV-1 by Binding to Heat Shock Element.Cells · 2022Article
- Catchet-MS identifies IKZF1-targeting thalidomide analogues as novel HIV-1 latency reversal agents.Nucleic acids research · 2022Article
- P-TEFb is degraded by Siah1/2 in quiescent cells.Nucleic acids research · 2022Article
- Novel role of UHRF1 in the epigenetic repression of the latent HIV-1.EBioMedicine · 2022Article
- Principles and Applications of CRISPR Toolkit in Virus Manipulation, Diagnosis, and Virus-Host Interactions.Cells · 2022Review
- Updates on CRISPR-based gene editing in HIV-1/AIDS therapy.Virologica Sinica · 2022Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The establishment of HIV-1 latency gives rise to persistent chronic infection that requires life-long treatment. To reverse latency for viral eradiation, the HIV-1 Tat protein and its associated ELL2-containing Super Elongation Complexes (ELL2-SECs) are essential to activate HIV-1 transcription. Despite efforts to identify effective latency-reversing agents (LRA), avenues for exposing latent HIV-1 remain inadequate, prompting the need to identify novel LRA targets. Here, by conducting a CRISPR interference-based screen to reiteratively enrich loss-of-function genotypes that increase HIV-1 transcription in latently infected CD4+ T cells, we have discovered a key role of the proteasome in maintaining viral latency. Downregulating or inhibiting the proteasome promotes Tat-transactivation in cell line models. Furthermore, the FDA-approved proteasome inhibitors bortezomib and carfilzomib strongly synergize with existing LRAs to reactivate HIV-1 in CD4+ T cells from antiretroviral therapy-suppressed individuals without inducing cell activation or proliferation. Mechanistically, downregulating/inhibiting the proteasome elevates the levels of ELL2 and ELL2-SECs to enable Tat-transactivation, indicating the proteasome-ELL2 axis as a key regulator of HIV-1 latency and promising target for therapeutic intervention.
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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.