ArticlePLoS pathogens2021
Intragenic proviral elements support transcription of defective HIV-1 proviruses.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 19 citations in OpenAlex.
- Intragenic transcription from defective HIV proviruses triggers interferon responses in myeloid cells.Journal of virology · 2026Article
- Smoldering in the sanctuary: HIV-associated brain injury in the ART era.The Journal of clinical investigation · 2026Review
- Bloom syndrome helicase is required for efficient HIV-1 reverse transcription in macrophages.bioRxiv : the preprint server for biology · 2026Article
- Intragenic Transcription from Defective HIV Proviruses Triggers Interferon Responses in Myeloid Cells.bioRxiv : the preprint server for biology · 2026Article
- Atlas of HIV cis-regulatory elements reveals extensive transcriptional variation across clades, isolates, and within individuals.bioRxiv : the preprint server for biology · 2026Article
- Review
- Inflammation at the maternal-fetal interface: a perspective on interacting risk factors for preterm birth in sub-Saharan African women living with HIV.Frontiers in immunology · 2026Review
- HIV reservoirs in lymphomagenesis: hidden driver in the era of viral suppression?Microbiology and molecular biology reviews : MMBR · 2025Review
- Immune Alterations and Viral Reservoir Atlas in SIV-Infected Chinese Rhesus Macaques.Infectious disease reports · 2025Review
- Neuroinflammation associated with proviral DNA persists in the brain of virally suppressed people with HIV.Frontiers in immunology · 2025Article
- Mu opioid receptor activation in microglia enhances HIV-1 infection and HIV-infection-induced inflammatory responses.Frontiers in immunology · 2025Article
- Specific quantification of inducible HIV-1 reservoir by RT-LAMP.Communications medicine · 2024Article
- Review
- The cell biology of HIV-1 latency and rebound.Retrovirology · 2024Review
- Plasma Human Immunodeficiency Virus 1 Soluble Glycoprotein 120 Association With Correlates of Immune Dysfunction and Inflammation in Antiretroviral Therapy-Treated Individuals With Undetectable Viremia.The Journal of infectious diseases · 2024Article
- Adaptation of a transmitted/founder simian-human immunodeficiency virus for enhanced replication in rhesus macaques.PLoS pathogens · 2023Article
- Virally Suppressed People Living with HIV Who Use Opioids Have Diminished Latency Reversal.Viruses · 2023Article
- Article
- Defective HIV-1 genomes and their potential impact on HIV pathogenesis.Retrovirology · 2022Review
- HIV-1 gp120 Impairs Spatial Memory Through Cyclic AMP Response Element-Binding Protein.Frontiers in aging neuroscience · 2022Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
HIV-1 establishes a persistent proviral reservoir by integrating into the genome of infected host cells. Current antiretroviral treatments do not target this persistent population of proviruses which include latently infected cells that upon treatment interruption can be reactivated to contribute to HIV-1 rebound. Deep sequencing of persistent HIV proviruses has revealed that greater than 90% of integrated HIV genomes are defective and unable to produce infectious virions. We hypothesized that intragenic elements in the HIV genome support transcription of aberrant HIV-1 RNAs from defective proviruses that lack long terminal repeats (LTRs). Using an intact provirus detection assay, we observed that resting CD4+ T cells and monocyte-derived macrophages (MDMs) are biased towards generating defective HIV-1 proviruses. Multiplex reverse transcription droplet digital PCR identified env and nef transcripts which lacked 5' untranslated regions (UTR) in acutely infected CD4+ T cells and MDMs indicating transcripts are generated that do not utilize the promoter within the LTR. 5'UTR-deficient env transcripts were also identified in a cohort of people living with HIV (PLWH) on ART, suggesting that these aberrant RNAs are produced in vivo. Using 5' rapid amplification of cDNA ends (RACE), we mapped the start site of these transcripts within the Env gene. This region bound several cellular transcription factors and functioned as a transcriptional regulatory element that could support transcription and translation of downstream HIV-1 RNAs. These studies provide mechanistic insights into how defective HIV-1 proviruses are persistently expressed to potentially drive inflammation in PLWH.
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