Lars Jørgen Østergaard

Broad activation of latent HIV-1 in vivo

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • Kirston Barton, Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, 176 Hawkesbury Road, Sydney, New South Wales 2145, Australia.
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  • Bonnie Hiener, Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, 176 Hawkesbury Road, Sydney, New South Wales 2145, Australia.
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  • Anni Winckelmann, Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, 176 Hawkesbury Road, Sydney, New South Wales 2145, Australia.
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  • Thomas Aagaard Rasmussen
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  • Wei Shao, Advanced Biomedical Computing Center, Leidos Biomedical Research Inc., PO Box B, Frederick, Maryland 21702, USA.
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  • Karen Byth, NWSLHD Research and Education Network, Darcy Road, Westmead, NSW 2145, Australia.
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  • Robert Lanfear, Department of Biological Sciences, Macquarie University, Sydney, New South Wales 2109, Australia.
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  • Ajantha Solomon, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, 792 Elizabeth Street, Melbourne, Victoria 3000, Australia.
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  • James McMahon, Department of Infectious Diseases, Alfred Hospital and Monash University, 55 Commercial Road, Melbourne, Victoria 3181, Australia.
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  • Sean Harrington, Ragon Institute of MGH, MIT, Harvard, 400 Technology Square, Cambridge, Massachusetts 02139, USA.
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  • Maria Buzon, Ragon Institute of MGH, MIT, Harvard, 400 Technology Square, Cambridge, Massachusetts 02139, USA.
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  • Mathias Lichterfeld, Ragon Institute of MGH, MIT, Harvard, 400 Technology Square, Cambridge, Massachusetts 02139, USA.
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  • Paul W Denton
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  • Rikke Olesen
  • Lars Jørgen Østergaard
  • Martin Tolstrup
  • Sharon R Lewin, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, 792 Elizabeth Street, Melbourne, Victoria 3000, Australia.
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  • Ole Schmeltz Søgaard
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  • Sarah Palmer, Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, 176 Hawkesbury Road, Sydney, New South Wales 2145, Australia.

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
JournalNature Communications
Volume7
Pages (from-to)12731
ISSN2041-1723
DOIs
Publication statusPublished - 2016

    Research areas

  • Journal Article

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ID: 102504370