ArticleProceedings of the National Academy of Sciences of the United States of America2016
Defective HIV-1 proviruses produce novel protein-coding RNA species in HIV-infected patients on combination antiretroviral therapy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 254 papers.
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Who cites it
254 citing papers in PubMed, 346 citations in OpenAlex.
- Virological and Immunological Outcomes of Combined Therapeutic Interventions and Dendritic Cell Therapy in People With HIV.The Journal of infectious diseases · 2025Trial
- Vedolizumab and ART in recent HIV-1 infection unveil the role of α4β7 in reservoir size.JCI insight · 2024Trial
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- Immunogenicity of personalized dendritic-cell therapy in HIV-1 infected individuals under suppressive antiretroviral treatment: interim analysis from a phase II clinical trial.AIDS research and therapy · 2022Trial
- Longitudinal study reveals HIV-1-infected CD4+ T cell dynamics during long-term antiretroviral therapy.The Journal of clinical investigation · 2020Trial
- Cell-associated HIV-1 RNA predicts viral rebound and disease progression after discontinuation of temporary early ART.JCI insight · 2020Trial
- Quantitative Human Immunodeficiency Virus (HIV)-1 Antibodies Correlate With Plasma HIV-1 RNA and Cell-associated DNA Levels in Children on Antiretroviral Therapy.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Trial
- The effects of antiretroviral therapy initiation time on HIV reservoir size in Chinese chronically HIV infected patients: a prospective, multi-site cohort study.BMC infectious diseases · 2019Trial
- Intragenic transcription from defective HIV proviruses triggers interferon responses in myeloid cells.Journal of virology · 2026Article
- Early intervention, lasting impact: benefits of early antiretroviral therapy and implications for posttreatment control.Current opinion in HIV and AIDS · 2026Review
- Article
- Coevolutionary dynamics of viruses and their defective interfering particles.PLoS computational biology · 2026Article
- Intragenic Transcription from Defective HIV Proviruses Triggers Interferon Responses in Myeloid Cells.bioRxiv : the preprint server for biology · 2026Article
- Undetectable unintegrated HIV-DNA in persons with HIV: frequency and determinants.BMC infectious diseases · 2026Article
- Dynamics of natural and pharmacologic control of an SIV variant with an envelope trafficking defect.The Journal of experimental medicine · 2026Article
- Article
- Immortalization and Targeted Enrichment of HIV-Infected CD4International journal of molecular sciences · 2026Article
- Genomic landscape of HIV-1 proviruses in ART-treated immunological non-responders.Frontiers in immunology · 2026Article
- Article
- Age-Associated Expansion of HIV/SIV Reservoirs in People With HIV and SIV-Infected Macaques.Aging cell · 2025Article
194 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
Despite years of plasma HIV-RNA levels <40 copies per milliliter during combination antiretroviral therapy (cART), the majority of HIV-infected patients exhibit persistent seropositivity to HIV-1 and evidence of immune activation. These patients also show persistence of proviruses of HIV-1 in circulating peripheral blood mononuclear cells. Many of these proviruses have been characterized as defective and thus thought to contribute little to HIV-1 pathogenesis. By combining 5'LTR-to-3'LTR single-genome amplification and direct amplicon sequencing, we have identified the presence of "defective" proviruses capable of transcribing novel unspliced HIV-RNA (usHIV-RNA) species in patients at all stages of HIV-1 infection. Although these novel usHIV-RNA transcripts had exon structures that were different from those of the known spliced HIV-RNA variants, they maintained translationally competent ORFs, involving elements of gag, pol, env, rev, and nef to encode a series of novel HIV-1 chimeric proteins. These novel usHIV-RNAs were detected in five of five patients, including four of four patients with prolonged viral suppression of HIV-RNA levels <40 copies per milliliter for more than 6 y. Our findings suggest that the persistent defective proviruses of HIV-1 are not "silent," but rather may contribute to HIV-1 pathogenesis by stimulating host-defense pathways that target foreign nucleic acids and proteins.
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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.