Background:  The novel anti-tumor promoting phorbol ester, prostratin, was evaluated for its ability to induce the expression of latent, HAART-persistent HIV-1 from specific sub-sets of patients' peripheral blood cells. 

Methods:        These studies were performed relative to the use of other cellular activating agents, such as OKT3, a monoclonal antibody against the human T-cell receptor, IL-2, PHA and p24 antigen (HIV-1-specific capsid protein), as well as a molecular relative of prostratin, 12-deoxyphorbol 13-phenylacetate (DPP).  PBMC of infected-individuals on virally-suppressive HAART were utilized. 

Results:          Prostratin performed as efficiently as the other cellular activators in inducing the expression of latent HIV-1 directly from the cells of patients on virally suppressive HAART.  Of interest was the induction of a novel species of latent virus from the cells of individuals after exposure to the HIV-1-specific capsid protein, p24, relative to virus expression induced by several other cell activators.  Cloning of the envelope glycoprotein sequences demonstrated that certain agents stimulated the production of specific replication-competent minor species within the proviral reservoir of these patients' PBMC, while other agents had a direct effect on stimulating the major archival species.  As such there appears to be an agent-specific induction and stimulation of selected latent reservoir viral strains. 

Conclusions:  These data also suggest that now a variety of complementary agents may be available for animal model studies of lentiviral latency and potential clinical use to broadly induce the expression of latent, HAART-persistent HIV-1 in vivo, with the goal of potential HIV-1 reservoir depletion.  As well, these studies provide critical molecular data on the apparent complexity of the in vivo HIV-1 reservoirs and persistent molecular states.

Keywords: Reservoirs; Latency; HAART