Curaxin CBL0137 has the potential to reverse HIV-1 latency

J Med Virol. 2019 Aug;91(8):1571-1576. doi: 10.1002/jmv.25487. Epub 2019 May 1.

Abstract

A cure for human immunodeficiency virus type-1 (HIV-1) has been hampered by the limitation of current combination antiretroviral therapy (cART) to address the latent reservoirs in HIV-1 patients. One strategy proposed to eradicate these reservoirs is the "shock and kill" approach, where latency-reversing agents (LRAs) are used to reactivate and promote viral cell death and/or immune killing of reactivated cells. Here, we report that curaxin CBL0137, an antitumor compound, can potentiate tumor necrosis factor-α-mediated reactivation of latently infected HIV-1cell lines. Additionally, the single use of CBL0137 is sufficient to reactivate HIV-1 latent reservoirs in peripheral mononuclear cells (PBMCs) isolated from HIV-1 positive, cART-treated, aviremic patients. Thus, CBL0137 possesses capabilities as a LRA and could be considered for the "shock and kill" approach.

Keywords: HIV-1 latency; curaxins; facilitates chromatin transcription complex; human immunodeficiency virus type 1; latency-reversing agents.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Carbazoles / pharmacology*
  • Cells, Cultured
  • HIV Infections / virology*
  • HIV-1 / physiology*
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / virology
  • Tumor Necrosis Factor-alpha / metabolism
  • Virus Activation / drug effects*
  • Virus Latency*

Substances

  • CBLC137
  • Carbazoles
  • Tumor Necrosis Factor-alpha