STRIPPING cholesterol from the surface of cells could be the key to making an
effective “chemical condom” that prevents cells being infected with HIV during
sex.
James Hildreth of Johns Hopkins University School of Medicine in Baltimore,
Maryland, and his team have found that the cholesterol that forms part of all
cell membranes helps the AIDS virus enter cells. Removing this cholesterol can
reduce infection rates by at least 90 per cent.
When a newly formed virus emerges from a human cell, it is coated with a bit
of the infected cell’s fatty membrane. Researchers assumed the virus tore off
bits of the membrane at random. But recent work by Hildreth and others has shown
this isn’t the case.
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It turns out that viruses make their escape at specific regions known as
lipid rafts—parts of cell membrane that contain proteins called adhesion
molecules. “By stealing these proteins from its host, HIV is able to bind to
other cells more easily,” says Hildreth.
Since lipid rafts seem to play such an important role in HIV’s escape from
cells, Hildreth’s team decided to see if they were also important in infection.
Lipid rafts contain high concentrations of fats such as cholesterol, which gives
the rafts their rigidity. So the researchers treated human cells with sugar
polymers called beta-cyclodextrins, which can pull cholesterol off membranes.
The treatment stopped adhesion proteins binding to these cells, showing that the
lipid rafts had been temporarily disrupted.
More importantly, preliminary experiments in mice suggest beta-cyclodextrins
can reduce vaginal HIV transmission by at least 90 per cent. “And I think we’ll
be able to improve that even more,” says Hildreth.
He hopes that a cream containing the sugar could prevent viral transmission
during sex. Health experts hope such chemical condoms will one day protect
people whose sexual partners refuse to wear condoms.
“I’m very excited about this work,” says Susan Plaeger, a viral immunologist
with the National Institute of Allergy and Infectious Diseases near Washington
DC. But she points out that lipid rafts are important to the health of human
cells.
Hildreth admits that removing cholesterol from cells is risky. But he points
out that beta-cyclodextrins are already used as solvents in some medicinal
creams. His mice experiments suggest the treatment is no more irritating to the
animal’s tissue than a dose of slightly salty water.
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More at:
AIDS Research and Human Retroviruses (vol 17, p 1009)