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Scientists Obtain New Information in the Study of AIDS - 2002-09-26


Scientists in New York have come closer to answering the mystery of why many people infected with the AIDS virus do not get sick. They have identified a long-suspected set of proteins that prevents HIV infection from developing into AIDS. The researchers are now working to turn their finding into an AIDS treatment.

Scientists have known since 1986 that immune system cells of certain people infected with HIV produce chemicals that somehow stop the virus from reproducing and progressing to AIDS. Despite extensive research by many groups, that factor, called CAF, has remained undiscovered for 16 years.

Now, a team at the Aaron Diamond AIDS Research Center in New York City says it has identified the proteins that make up at least part of the protective CAF. The group reports in the journal Science that immune cells, known as CD8 cells, taken from non-progressing HIV patients secrete three defensive molecules called defensins that inhibited replication of HIV in laboratory cell cultures.

Aaron Diamond scientist David Ho calls the results conclusive.

"We are most gratified that this work has helped to solve a big part of the mystery surrounding CAF that's been around for so long," he said. "There is very little question based on our data that defensins are a major contributor to CAF activity."

The researchers found that when they removed the defensin proteins from the CD8 immune cells in the laboratory, the cells lost their ability to block HIV reproduction.

They say their discovery is a major step toward understanding how the body fights the AIDS virus.

But several leading AIDS researchers are not convinced that defensins are key. Science magazine quotes Harvard Medical School investigator Bruce Walker as saying the new data show that the proteins have only a very modest effect against HIV. Mr. Walker's lab recently described another candidate as the CAF factor.

A co-discoverer of the AIDS virus, Robert Gallo of the Institute of Human Virology in Baltimore, takes exception to the idea that a single CAF factor exists.

In a news briefing Thursday, David Ho did not claim that his team had discovered the entire answer to the mystery.

"We just hope to open up a new avenue of research," he said. "This is not going to be the ultimate solution, but it's another weapon we could use in our arsenal against HIV."

The Aaron Diamond Center group has begun what they predict will be a years-long process of determining whether defensins can be translated into an AIDS treatment or even a compound to prevent infection.

First, they want to learn which of the several subtypes of CD8 cells secrete them. Because the defensin molecules are very large, they want to identify which parts are active against HIV in order to design a smaller therapeutic molecule, which is more likely to be absorbed when injected.

"I want to be cautious not to lead people to think that automatically a therapy or prophylactic will evolve from here in a short period of time."