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Health Wire Reuters Prostratin potential agent can activate latent HIV, permitting eradication

By Karla Gale

(Reuters)--Prostratin can induce HIV expression from latently infected CD4+ cells without subsequent infection of surrounding cells and may allow elimination of the infected cells, according to California researchers.

Prostratin is a phorbol ester isolated from a plant in Samoa used as a traditional remedy for illnesses such as yellow fever, the researchers note in their report in the Journal of Virology for August. Previous research has demonstrated prostratin's ability to activate HIV replication in latently infected cell cultures, but data were lacking regarding its characteristics in latently infected primary T cells.

To that end, Dr. Jerome A. Zack, of the UCLA AIDS Institute in Los Angeles, and colleagues evaluated results using purified quiescent T cells from healthy HIV-seronegative blood donors and latently infected T cells extracted from humanized immunodeficient mice.

"We found that prostratin induces cells to express viral protein, but it does not cause global proliferation of resting T cells," Dr Zack told Reuters Health. He added that the signal transmitted by prostratin is sufficient to activate the expression of virus integrated into host-cell DNA without inducing cell cycle progression on its own, or allowing de novo infection of surrounding cells to take place.

He speculates that once patients are established on effective antiretroviral therapy, they could be treated with an agent like prostratin to activate latent reservoirs. The immune response could then be boosted with a vaccine or an immunotoxin to knock out the reservoir.

This strategy is "still in a theoretical realm," Dr. Zack cautioned. He and his associates are now planning experiments in nonhuman primates with simian immunodeficiency virus to further investigate the potential of prostratin.

One caveat, he noted, is that there may be "other reservoirs besides latently infected T cells, such as microglia," which would require agents with the ability to pass the blood-brain barrier. For now, his group's goal is to "work stepwise, eliminating virus from one major reservoir at a time."

08/14/02

For more information, contact Irl. S. Barefield, Executive Director of AIDS ReSearch Alliance, or Stephen J. Brown, Director of Clinical Research at AIDS ReSearch Alliance.

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