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Cholesterol May Be HIV's Achilles' Heel

Study: Depriving virus of fatty nutrient could help stop spread

FRIDAY, July 27, 2001 (HealthDayNews) -- The cholesterol that's an essential part of cell walls could be the Achilles' heel of the AIDS virus, new research shows.

Scientists say compounds that strip cells of that cholesterol not only protect them against HIV infection but also appear to defang the virus. The double-acting chemicals one day could make their way into topical creams, lubricants or other products to guard against sexually-acquired HIV.

"We are convinced that these molecules, appropriately formulated, will be a safe and effective microbicide to block HIV during sexual intercourse," says Dr. James Hildreth, a Johns Hopkins University pharmacologist who led the research. A report on the findings appears in the latest issue of the journal AIDS Research and Human Retroviruses.

The work builds on an earlier finding by Hildreth and his colleagues that HIV's exited infected cells on stiff clusters of fatty molecules, called lipid rafts, which float in the otherwise more liquid membrane. Hildreth's team wondered if, in the process, the virus picked up some cholesterol on its way out. If HIV did take cholesterol, they reasoned, then the fat might be an important nutrient for the virus, as it is for other microbes.

In the latest study, the researchers took both cultured cells and samples from human donors and treated them with compounds called cyclodextrins that trap cholesterol in little doughnuts of sugars. When exposed to HIV, the cells did not become infected with the virus. The chemicals also shielded them from SIV, the monkey version of the virus.

Cyclodextins appear to keep HIV at bay by loosening the structure of chemokine receptors, molecular locks that the virus must hook up with to pass into the cell interior.

But in another set of experiments Hildreth's group found that depriving HIV of cholesterol cripples the virus itself. "Quite remarkably, the compound has the ability to inactivate HIV at multiple levels. It renders cells unsusceptible to HIV and it also inactivates the virus."

Marilyn Resh, an HIV expert at Memorial Sloan-Kettering Cancer Center in New York City, who is also exploring lipid rafts, says any treatment based on depriving cells of cholesterol could run into problems. "Many normal cell functions are highly dependent on the integrity of lipid rafts," particularly the T-cell receptors that play a crucial role in fighting infection, Resh says.

However, Hildreth says other Hopkins researchers have tested a solution with cyclodextrins in the vaginal tissue of female mice and found that it leaves at least their outer cell layers intact. What's more, he says the compounds are widely used in pharmaceuticals as chaperones to help drugs enter fat-rich cells. "It appears that they're safe based on their use in humans already."

What To Do

For an explanation of lipid chemistry, check the DiscoverySchool.

To learn more about HIV and AIDS, visit the University of California at San Francisco or the American Medical Association.

SOURCES: Interviews with James Hildreth, M.D., Ph.D., associate professor of pharmacology, Johns Hopkins University School of Medicine, Baltimore, and Marilyn Resh, Ph.D., head of biochemical and molecular virology, Memorial Sloan-Kettering Cancer Center, New York City; July 20, 2001, AIDS Research and Human Retroviruses
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