Lars Jørgen Østergaard

HDAC inhibition induces HIV-1 protein and enables immune-based clearance following latency reversal

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

  • Guoxin Wu, Department of Pulmonary Medicine and Infectious Disease
  • ,
  • Michael Swanson, Department of Biologics and Vaccine Formulations, Merck & Co. Inc., Kenilworth, New Jersey, USA.
  • ,
  • Aarthi Talla, Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
  • ,
  • Donald Graham, Department of Pulmonary Medicine and Infectious Disease
  • ,
  • Julie Strizki, Department of Pulmonary Medicine and Infectious Disease
  • ,
  • Daniel Gorman, Department of Biologics, Merck & Co. Inc., Kenilworth, New Jersey, USA.
  • ,
  • Richard Jo Barnard, Department of Pulmonary Medicine and Infectious Disease
  • ,
  • Wade Blair, Department of Pulmonary Medicine and Infectious Disease
  • ,
  • Ole S Søgaard
  • ,
  • Martin Tolstrup
  • Lars Østergaard
  • Thomas A Rasmussen
  • ,
  • Rafick-Pierre Sekaly, Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
  • ,
  • Nancie M Archin, University of North Carolina (UNC) HIV Cure Center, UNC Chapel Hill, Chapel Hill, North Carolina, USA.
  • ,
  • David M Margolis, University of North Carolina (UNC) HIV Cure Center, UNC Chapel Hill, Chapel Hill, North Carolina, USA.
  • ,
  • Daria J Hazuda, Department of Pulmonary Medicine and Infectious Disease
  • ,
  • Bonnie J Howell, Department of Pulmonary Medicine and Infectious Disease

Promising therapeutic approaches for eradicating HIV include transcriptional activation of provirus from latently infected cells using latency-reversing agents (LRAs) and immune-mediated clearance to purge reservoirs. Accurate detection of cells capable of producing viral antigens and virions, and the measurement of clearance of infected cells, is essential to assessing therapeutic efficacy. Here, we apply enhanced methodology extending the sensitivity limits for the rapid detection of subfemtomolar HIV gag p24 capsid protein in CD4+ T cells from ART-suppressed HIV+ individuals, and we show viral protein induction following treatment with LRAs. Importantly, we demonstrate that clinical administration of histone deacetylase inhibitors (HDACis; vorinostat and panobinostat) induced HIV gag p24, and ex vivo stimulation produced sufficient viral antigen to elicit immune-mediated cell killing using anti-gp120/CD3 bispecific antibody. These findings extend beyond classical nucleic acid endpoints, which are confounded by the predominance of mutated, defective proviruses and, of paramount importance, enable assessment of cells making HIV protein that can now be targeted by immunological approaches.

Original languageEnglish
Article numbere92901
JournalJCI Insight
Volume2
Issue16
Number of pages12
ISSN2379-3708
DOIs
Publication statusPublished - 17 Aug 2017

    Research areas

  • Journal Article

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