HIV Stymied by New Molecule

The much-celebrated advances made last year in understanding how HIV wangles its way into cells have led to the discovery of what may be a new way to thwart the virus. In this week's issue of Science,* researchers describe a molecule, modified from a naturally occurring immune messenger, that seems exceptionally capable of preventing HIV from entering uninfected cells--at least in the test tube.

The work builds on a flood of findings published last year that linked HIV and chemokines, the family of inflammation-promoting chemicals to which the new molecule, called AOP-RANTES, belongs. Researchers have known for more than a decade that HIV slips into white blood cells using a receptor found on their surface known as CD4, but it appeared to need some other coreceptor, too. Last year, the missing player turned out to be the cell-surface molecules that normally serve as receptors for chemokines. Since then, many researchers have begun exploring ways to prevent HIV infection by blocking chemokine receptors.

While some AIDS researchers believe that injections of chemokines themselves may safely block HIV infection, others worry that such treatments might cause severe inflammation. To get around this possible side effect, a team of researchers from the Chester Beatty Laboratories in London, the Geneva division of drugmaker Glaxo Wellcome, and the Laboratory for Molecular Pharmacology in Copenhagen have modified the chemokine RANTES so that it can bind to the receptor without triggering an inflammatory response.

The new molecule appears to have much more potent anti-HIV powers than does RANTES--which itself has the most potent anti-HIV affects of any natural chemokine--by tying up more receptors. "This particular compound is a stronger inhibitor than anything [similar] shown so far," says Robin Weiss, who heads the lab at Chester Beatty in which several of the paper's co-authors work. What's more, AOP-RANTES works both in immune cells known as T cells and in macrophages, whereas RANTES only works in T cells.

Experts in the field are reacting with guarded optimism. "What they found may well be a pretty good drug--if they can keep levels high enough in the body for 24 hours a day, 7 days a week," says chemokine researcher Craig Gerard of Harvard University. That, of course, has proven to be an insurmountable "if" for many other promising compounds. Even Weiss, whose lab has been fielding media calls all day, worries that the work "is being hyped up too much."

For more details, Science Online subscribers can link to the full text of the Report.

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