Vorinostat Renders the Replication-Competent Latent Reservoir of Human Immunodeficiency Virus (HIV) Vulnerable to Clearance by CD8 T Cells

EBioMedicine. 2017 Sep;23:52-58. doi: 10.1016/j.ebiom.2017.07.019. Epub 2017 Jul 29.

Abstract

Latently human immunodeficiency virus (HIV)-infected cells are transcriptionally quiescent and invisible to clearance by the immune system. To demonstrate that the latency reversing agent vorinostat (VOR) induces a window of vulnerability in the latent HIV reservoir, defined as the triggering of viral antigen production sufficient in quantity and duration to allow for recognition and clearance of persisting infection, we developed a latency clearance assay (LCA). The LCA is a quantitative viral outgrowth assay (QVOA) that includes the addition of immune effectors capable of clearing cells expressing viral antigen. Here we show a reduction in the recovery of replication-competent virus from VOR exposed resting CD4 T cells following addition of immune effectors for a discrete period.

Take home message: VOR exposure leads to sufficient production of viral protein on the cell surface, creating a window of vulnerability within this latent reservoir in antiretroviral therapy (ART)-suppressed HIV-infected individuals that allows the clearance of latently infected cells by an array of effector mechanisms.

Keywords: Eradication; HIV; Immune effector; Latency; Vorinostat.

MeSH terms

  • Antigens, Viral / immunology
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • CD4-CD8 Ratio
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / virology*
  • HIV-1 / drug effects*
  • HIV-1 / physiology*
  • HLA Antigens / immunology
  • Humans
  • Hydroxamic Acids / pharmacology*
  • Peptides / immunology
  • Viral Load
  • Virus Latency / drug effects*
  • Virus Latency / immunology
  • Virus Replication / drug effects*
  • Virus Replication / immunology
  • Vorinostat

Substances

  • Antigens, Viral
  • HLA Antigens
  • Hydroxamic Acids
  • Peptides
  • Vorinostat