Broad activation of latent HIV-1 in vivo

Kirston Barton, Bonnie Hiener, Maria Buzon, Mathias Lichterfeld, Paul W. Denton, Rikke Olesen, Lars Østergaard, Martin Tolstrup, Sharon R. Lewin, Ole Schmeltz Søgaard, Sarah Palmer, Anni Winckelmann, Thomas Aagaard Rasmussen, Wei Shao, Karen Byth, Robert Lanfear, Ajantha Solomon, James McMahon, Sean Harrington

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    62 Citations (Scopus)
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    The 'shock and kill' approach to cure human immunodeficiency virus (HIV) includes transcriptional induction of latent HIV-1 proviruses using latency-reversing agents (LRAs) with targeted immunotherapy to purge infected cells. The administration of LRAs (panobinostat or vorinostat) to HIV-1-infected individuals on antiretroviral therapy induces a significant increase in cell-associated unspliced (CA-US) HIV-1 RNA from CD4⁺ T cells. However, it is important to discern whether the increases in CA-US HIV-1 RNA are due to limited or broad activation of HIV-1 proviruses. Here we use single-genome sequencing to find that the RNA transcripts observed following LRA administration are genetically diverse, indicating activation of transcription from an extensive range of proviruses. Defective sequences are more frequently found in CA HIV-1 RNA than in HIV-1 DNA, which has implications for developing an accurate measure of HIV-1 reservoir size. Our findings provide insights into the effects of panobinostat and vorinostat as LRAs for latent HIV-1.
    Original languageEnglish
    Pages (from-to)12731-1-12731-8
    Number of pages8
    JournalNature Communications
    Publication statusPublished - 2016

    Bibliographical note

    Copyright the Author(s) 2016. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


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