Reuters 27/09/2002 06:09 PM Maggie Fox, Health and Science Correspondent

AIDS researchers said they had identified a long sought-after substance that allows a small number of people to naturally live with the AIDS virus for decades without ever getting ill.

They hope they can use the compound, consisting of three proteins called alpha-defensins, to design better drugs to fight the HIV virus, which infects 40 million people worldwide and has killed 25 million.

"This is not going to be the ultimate solution but it is another weapon we can use in our arsenal against HIV," Dr. David Ho of the Aaron Diamond AIDS Research Center at Rockefeller University in New York, who helped lead the study, told reporters in a telephone briefing.

The proteins are made by immune system cells called CD8 T-cells, and help block the activity of the deadly and incurable virus. For 16 years researchers have known that CD8 cells in certain HIV-infected patients were making something unique, but they did not know precisely what it was.

These patients, called long-term non-progressors, can be infected for years and even decades without ever developing the symptoms of AIDS. AIDS specialists have been studying them to find out what is different about their bodies.

Ho, Linqi Zhang and colleagues used a protein chip to identify the three alpha-defensins.

They are not sure yet exactly how the three proteins block the virus, but are doing experiments now to find out.

Other AIDS researchers say Ho's study, published in the journal Science, did not explain the whole story of long-term non-progressors. Their immune system also makes compounds called beta-chemokines, which also help block HIV.

HELPS UNDERSTANDING

But Dr. Robert Siciliano of Johns Hopkins University in Baltimore, a leading HIV researcher, said the study answers many questions.

"It has been unclear what all of the components of this activity, this antiviral activity are, and this helps us understand more about it," he said in a telephone interview.

The Aaron Diamond team said that when they took away the beta-chemokines and the alpha-defensins, the CD8 cells of long-term non-progressors seemed just as vulnerable to HIV as anyone else's.

Long term non-progressors are not immune to HIV. Their CD8 cells cut the activity of HIV by between 40 and 60 percent, and eventually they do start to become ill.

HIV patients now can take a cocktail of drugs called highly active antiretroviral therapy or HAART, which can keep them well for years. But the drugs are not a cure, have serious side-effects, are expensive and eventually the virus infecting each patient mutates so that they do not work as well.

Ho said a protein chip made by Fremont, California-based Ciphergen made the work on CD8 cells possible. Such a "chip" works by identifying the proteins made by a cell, using a mass spectrometer.

"Basically we came at the old question with a new tool," Ho said.

They figured out the weight and part of the structure of the proteins, and looked them up in the library of known proteins.

"We could search the literature and take a pretty good guess that the cluster consisted of alpha defensins 1, 2 and 3," Ho said. These alpha-defensin proteins work in the immune system and are believed to punch holes in the cell membranes of bacteria, killing them.

"They were found principally in one kind of white blood cell called a neutrophil. These cells are responsible for gobbling up bacteria and killing them," Ho said.

Ho stressed that much more work needs to be done.

"We wish to be somewhat cautious. I think it is not entirely clear whether we could take this discovery and turn it into a useful therapy," he said.

The proteins are too large to use as a drug, so it would be better to examine precisely which part of them is doing the work against HIV and develop that as a drug, Ho said.

-- Anonymous, September 27, 2002