Expression of latent HAART-persistent HIV type 1 induced by novel cellular activating agents.
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.
Kulkosky
Joseph
J
Center for Human Virology and Biodefense, Division of Infectious Diseases and Environmental Medicine, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. Joseph.Kulkosky@chc.edu
Sullivan
Julie
J
Xu
Yan
Y
Souder
Emily
E
Hamer
Dean H
DH
Pomerantz
Roger J
RJ
D000595:Amino Acid Sequence; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D016655:HIV Core Protein p24 / Q000494:pharmacology; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D016853:Muromonab-CD3 / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology
D016655:HIV Core Protein p24; D016853:Muromonab-CD3; D010703:Phorbol Esters; D010835:Phytohemagglutinins; C070999:prostratin