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Defensins Inhibit HIV

Researchers at Rockefeller University in the Aaron Diamond AIDS Research Center (ADARC) in New York have identified proteins that inhibit the human immunodeficiency virus using mass spectrometry.

Scientists may have finally identified an elusive protein that allows some people to remain healthy for many years after being infected by the virus that causes AIDS. The discovery could lead to a new approach to fighting the deadly disease.

AIDS researchers have been intrigued for sometime as to why 1-5% of patients infected by HIV can live for 10 or 15 years, or even longer, with no apparent damage to their immune systems. Dr. Robert Lehrer, a professor of medicine at UCLA, who led the discovery of human defensins in the 1980s first noticed that certain immune cells (CD8 T-cells) in these patients seemed to produce some protective factor. Since then scientists have been working to identify the factor(s).

In the mid-1990s, a group of compounds known as beta-chemokines were discovered that suppressed some, but not all, types of the virus. The New York scientists, led by Dr. Linqi Zhang, think the defensins account for most of the rest of the protective factor.

Using the selective isolation of these proteins on a chip, the researchers used mass spectrometry to measure the molecular weights of the proteins and their fragments to search a database of known proteins.

Three proteins, alpha-defensins 1, 2, and 3, appear to work in combination to prevent the virus' replication, or copying, in the body. Defensins were first described by scientists Ganz and Lehrer in 1985 and were thought to be made exclusively by neutrophils, a specialized immune system cell, to kill bacteria. The Rockefeller/ADARC researchers have found that they are also made by CD8+ T-cells and inhibit the replication of HIV by an as-yet-undetermined mechanism.

One application already being worked on is a test if infected people have CD8 T-cells make defensins before putting the proteins to work in a treatment.

The authors note that using defensins as a medicine might be difficult, in part because they are difficult to manufacture outside the cell. "This is not going to be the ultimate solution, but it's another weapon we can use in our arsenal against HIV," said Dr. David Ho, the Director of the Aaron Diamond AIDS Research Center in New York.

The full report appears in the September 26 issue of
Science Express.



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