Researchers Find Method to Study Hidden HIV Reservoirs

Scientists are now one step closer to understanding how HIV hides in cells and reemerges once patients stop taking combination drug therapy. The phenomenon reflects the existence of hidden populations of latently infected cells. As a result, patients must remain on therapy for life. Gladstone Institute of Virology and Immunology researchers have found a way to identify and study latently infected cells in the laboratory.

"Our work is geared toward finding a way to obliterate this latent pool, which would take us closer to actually finding a cure for AIDS," said senior author Eric Verdin, MD, senior investigator at Gladstone and a University of California-San Francisco professor of medicine.

The researchers constructed a recombinant HIV strain carrying a green fluorescent protein. Using this marker, they identified a small fraction of infected cells in which the virus was latent. These cells represented less than 1 percent of the infected population and had eluded purification until this study.

The Gladstone researchers found that, in latently infected cells, the HIV genome is integrated into transcriptionally inactive regions of DNA called heterochromatin. Verdin and colleagues are trying to identify drugs that can activate latent cells and cause them to produce virus. A preliminary screen identified a number of compounds that can reactivate latent HIV in the laboratory.

"Hopefully, we will be soon in a position to test some of these compounds in an animal model infected with a virus related to HIV," Verdin said. "This will allow us to determine whether the 'flushing' of latent pools is a viable therapeutic approach in HIV infection." The full study, "HIV Reproducibly Establishes a Latent Infection After Acute Infection of T Cells in Vitro" is published in the April 15 issue of European Molecular Biology Organization Journal (2003;22(8):1868-1877).

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