New AIDS-Fighting Chemicals Identified

For the first time, scientists have identified human proteins that may stifle AIDS by keeping HIV from reproducing in the body. The discovery might not only explain why some people with HIV remain healthy for decades, but also lead someday to new AIDS-combating treatments.

"This is something that we're studying not just for therapy, but for preventing the infection in the first place," said researcher David Ho of the Aaron Diamond AIDS Research Center in New York. About 1 to 2 percent of the 850,000-900,000 people with HIV in the United States remain healthy for many years without developing AIDS, Ho said. The findings were published in the online edition of Science (Sept. 27, 2002;297;5590).

Since 1986, scientists have known that certain white blood cells in HIV-infected, AIDS-free patients secrete biochemicals that somehow prevent HIV's replication, but the identity of the substance has proven a mystery. Because it comes from the CD8 T cells that kill infection in the body, the compound was labeled CD8 antiviral factor, or CAF. In 1995, "it seemed the mystery was solved," Ho said, by beta-chemokines, which suppress HIV to a degree. But investigators found beta-chemokines could not explain much of CAF's protective power because they were ineffective against many viral strains.

Now, using sensitive new protein analyzers, lead researcher Linqi Zhang, Ho and team found all AIDS-free HIV-infected patients studied secreted three chemicals that were absent in people developing AIDS. Experiments and database searches revealed these chemicals were the antibodies alpha-defensins-1, -2 and -3, which also attack herpes and flu viruses.

Purified human versions of alpha-defensins reduced HIV replication by 50 to 60 percent, although Ho said it seems a minimum of two alpha-defensin types working together are necessary for anti-HIV activity. Synthetic alpha-defensins also reduced HIV activity, although they were 10 to 20 times weaker than the natural versions. The proteins do not seem to attack the surface of HIV, as they do herpes and flu viruses. Because the alpha-defensins are relatively large molecules, they can be cumbersome to use, Ho said.

"By understanding how some people's immune systems are able to control HIV infection, we may be able to develop new treatments that take advantage of this phenomenon," Zhang said.

Susan Plaeger, chief of the National Institute of Allergy and Infectious Disease's AIDS research branch, found the work "exciting, but I don't think it's the absolute answer." "I don't know if these molecules are definitely responsible for the activity of CAF. But this is very good work that needs to be followed up. There could definitely be other factors bound up here."

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