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Researchers Find AIDS Virus’ Precise Target on White Blood Cells

June 2, 1988

PASADENA, Calif. (AP) _ Scientists have identified the precise target where the AIDS virus latches onto cells it destroys, another step toward a drug to combat the fatal disease.

″For the first time, we have fairly precisely defined the structure on the cell surface to which a virus binds. This is a primary step in the infective process,″ said protein chemist Stephen B.H. Kent, research team leader at the California Institute of Technology.

Once the virus’ target, called a ″binding site,″ was identified by Caltech molecular biologist Bradford Jameson, the study’s chief author, he and his colleagues manufactured crude synthetic copies of the binding site.

The study’s co-authors at the University of Alabama then found that in the test tube, the fake binding sites acted as decoys to attract the AIDS virus. They overwhelmed AIDS virus particles so the virus couldn’t latch onto real binding sites on T4 white blood cells, the main cells infected and destroyed by the virus, which cripples the immune system.

If scientists can create more sophisticated versions of the fake binding site, those might work as a drug to treat or cure acquired immune deficiency syndrome, or to carry virus-killing drugs to the AIDS virus.

The same method might be used to create drugs to fight other viruses, rheumatoid arthritis and rejection of transplanted organs, Jameson said.

″This is the first step toward a second-generation drug″ that could be available in 10 years and be more effective than drugs now under development to combat the AIDS virus, Kent said, adding, ″We do not want to give people false hope.″

″Kent is exaggerating the length of time a little bit,″ said Dr. Mathilde Krim, a founder of the American Foundation for AIDS Research. ″If things go very well, I’d say two years until it (the drug) would be made available to people with life-threatening HIV (AIDS virus) infection.″

Krim’s foundation funded the $120,000 study, which is being published Friday in the journal Science. Other co-authors included ORTHO Pharmaceuticals researchers in Raritan, N.J.

Scientists previously knew the AIDS virus infects T4 white blood cells by binding to CD4, a protein on their surface. Caltech researchers identified the exact part of that protein to which the AIDS virus binds, and determined that it looks like a loop protruding from the protein.

″To my knowledge, it is the first time a binding site has been identified with such precision for any virus,″ Krim said by phone from New York. ″It’s a wonderful accomplishment.″

″It will enable people to get a handle on the mechanism by which a virus can infect a cell,″ Jameson said.

In December, researchers at Philadelphia’s Smith Kline & French Laboratories, South San Francisco’s Genentech Inc. and Boston’s Dana Farber Cancer Institute said they manufactured synthetic CD4 proteins. In test-tube experiments, the fake proteins acted as decoys, preventing the AIDS virus from infecting T4 cells.

The fake binding site copies made by Jameson, Kent and Caltech biology chairman Leroy Hood stopped AIDS infection the same way. Kent speculated that a drug made only of fake binding sites, rather than fake whole CD4 proteins, should last longer in the bloodstream and be more effective in stopping AIDS.

A major obstacle is that either fake CD4 proteins or fake binding sites might serve not only as decoys for the AIDS virus, but as decoys for macrophages, cells that carry invading germs to T4 cells so they can be destroyed by the immune system.

So a drug meant to prevent AIDS from destroying the immune system might actually prevent the immune system from performing its job, Kent said.

But Krim said that risk should be much lower if fake binding sites rather than fake CD4 proteins are used in a drug, and that such risk would be acceptable in treating severely ill AIDS patients.

Kent said drugs could be developed against other viruses if scientists identify precisely binding sites on cells those viruses attack, then make fake binding sites to prevent the viruses from reaching their intended targets.

Such drugs might be useful even if they harm the immune system. Those drugs might be used to treat rheumatoid arthritis and other ″autoimmune″ diseases - in which the body is attacked by its own immune system - and to prevent the immune system from rejecting transplanted organs, Krim and Jameson said.

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