Expression of latent HAART-persistent HIV type 1 induced by novel cellular activating agents

AIDS Res Hum Retroviruses. 2004 May;20(5):497-505. doi: 10.1089/088922204323087741.

Abstract

The novel antitumor-promoting phorbol ester, prostratin, was evaluated for its ability to induce the expression of latent, highly active antiretroviral therapy (HAART)-persistent human immunodeficiency virus type I (HIV-1) from specific subsets of patients' peripheral blood cells. This evaluation was performed relative to the use of other cellular activating agents, such as OKT3, a monoclonal antibody against the human T cell receptor, interleukin-2 (IL-2), phytohemagglutinin (PHA), p24 antigen (HIV-1-specific capsid protein), and a molecular relative of prostratin, 12-deoxyphorbol 13-phenylacetate (DPP). Prostratin performed as efficiently as the other cellular activators at inducing the expression of latent HIV-1 from cells of patients on virally suppressive HAART. Of interest was the induction of a novel species of latent virus from the cells of an individual after exposure to the HIV-1-specific capsid protein, p24, relative to virus expression induced by several other cell activators. This suggests that a variety of agents may be available for animal model studies of lentiviral latency and clinical use to broadly induce the expression of latent, HAART-persistent HIV-1 in vivo with the goal of potential HIV-1 reservoir depletion or eradication.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antiretroviral Therapy, Highly Active*
  • CD4-Positive T-Lymphocytes / cytology
  • HIV Core Protein p24 / pharmacology
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV-1 / drug effects*
  • Humans
  • Molecular Sequence Data
  • Muromonab-CD3 / pharmacology
  • Phorbol Esters / pharmacology
  • Phytohemagglutinins / pharmacology

Substances

  • HIV Core Protein p24
  • Muromonab-CD3
  • Phorbol Esters
  • Phytohemagglutinins
  • prostratin