Expression of Latent, HAART-Persistent HIV-1 Induced by Novel Cellular Activating Agents.

Roger J. Pomerantz, Julie Sullivan, Yan Xu, Emily Souder, Dean H. Hamer, and Joseph Kulkosky. Center for Human Virology and Biodefense, Thomas Jefferson University, Philadelphia, Pennsylvania (USA)

The novel anti-tumor 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-II (IL-2), phytohemagluttinin (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.