ArticleProceedings of the National Academy of Sciences of the United States of America2019
Combined HIV-1 sequence and integration site analysis informs viral dynamics and allows reconstruction of replicating viral ancestors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 106 citations in OpenAlex.
- Antigen Stimulation Reactivates HIV-1 Proviruses Despite Integration in Repressive Chromatin.bioRxiv : the preprint server for biology · 2026Article
- Positioning HIV SMRTcap within the HIV reservoir toolbox.PLoS pathogens · 2026Article
- Development and Evaluation of a Novel Relatively Low-Cost Method to Derive HIV-1 Integration Sites and Proviral Sequences.Viruses · 2026Article
- Immune correlates of HIV-1 rebound during broadly neutralizing antibody treatment in young children.The Journal of clinical investigation · 2026Article
- Dynamics of natural and pharmacologic control of an SIV variant with an envelope trafficking defect.The Journal of experimental medicine · 2026Article
- Article
- Early pandemic HIV-1 integration site preferences differ across anatomical sites.Communications medicine · 2025Article
- Elucidating the mechanism by which HIV-1 nucleocapsid mutations confer resistance to integrase strand transfer inhibitors.Science advances · 2025Article
- Impacts of immune checkpoint inhibitors use on the HIV reservoir are linked to provirus sequences but not integration sites.Scientific reports · 2025Article
- Immune-mediated strategies to solving the HIV reservoir problem.Nature reviews. Immunology · 2025Review
- Elucidating the Mechanism by Which HIV-1 Nucleocapsid Mutations Confer Resistance to Integrase Strand Transfer Inhibitors.bioRxiv : the preprint server for biology · 2025Article
- Divergent populations of HIV-infected naive and memory CD4+ T cell clones in children on antiretroviral therapy.The Journal of clinical investigation · 2025Article
- Comparing acute versus AIDS ART initiation on HIV-1 integration sites and clonal expansion.Signal transduction and targeted therapy · 2025Article
- A simple phylogenetic approach to analyze hypermutated HIV proviruses reveals insights into their dynamics and persistence during antiretroviral therapy.Virus evolution · 2025Article
- Distinguishable topology of the task-evoked functional genome networks in HIV-1 reservoirs.iScience · 2024Article
- Viral genome sequencing methods: benefits and pitfalls of current approaches.Biochemical Society transactions · 2024Review
- Article
- A simple phylogenetic approach to analyze hypermutated HIV proviruses reveals insights into their dynamics and persistence during antiretroviral therapy.Research square · 2024Article
- Immune targeting of HIV-1 reservoir cells: a path to elimination strategies and cure.Nature reviews. Microbiology · 2024Review
- Epistatic pathways can drive HIV-1 escape from integrase strand transfer inhibitors.Science advances · 2024Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
30 authors at 6 institutions in 2 countries.
Funding
Abstract
Understanding HIV-1 persistence despite antiretroviral therapy (ART) is of paramount importance. Both single-genome sequencing (SGS) and integration site analysis (ISA) provide useful information regarding the structure of persistent HIV DNA populations; however, until recently, there was no way to link integration sites to their cognate proviral sequences. Here, we used multiple-displacement amplification (MDA) of cellular DNA diluted to a proviral endpoint to obtain full-length proviral sequences and their corresponding sites of integration. We applied this method to lymph node and peripheral blood mononuclear cells from 5 ART-treated donors to determine whether groups of identical subgenomic sequences in the 2 compartments are the result of clonal expansion of infected cells or a viral genetic bottleneck. We found that identical proviral sequences can result from both cellular expansion and viral genetic bottlenecks occurring prior to ART initiation and following ART failure. We identified an expanded T cell clone carrying an intact provirus that matched a variant previously detected by viral outgrowth assays and expanded clones with wild-type and drug-resistant defective proviruses. We also found 2 clones from 1 donor that carried identical proviruses except for nonoverlapping deletions, from which we could infer the sequence of the intact parental virus. Thus, MDA-SGS can be used for "viral reconstruction" to better understand intrapatient HIV-1 evolution and to determine the clonality and structure of proviruses within expanded clones, including those with drug-resistant mutations. Importantly, we demonstrate that identical sequences observed by standard SGS are not always sufficient to establish proviral clonality.
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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.