Among the most vexing puzzles of the AIDS virus is why it kills some people quickly but allows others to live for decades without damage to their immune system. Now a team led by Linqi Zhang and David Ho of the Aaron Diamond AIDS Research Center in New York City claims to have found the reason: three tiny molecules called a-defensins. But other researchers who have been digging for answers say they're not throwing away their shovels yet.
In the early days of the AIDS epidemic, virologist Jay Levy of the University of California, San Francisco, proposed that immune system cells secrete a chemical that can stop HIV. Levy's theory led to a 16-year hunt for the so-called CD8 antiviral factor (CAF).
Now, a team of scientists proposes that they've identified the elusive CAF as defensins. Defensins are proteins secreted primarily by white blood cells called neutrophils that break down bacterial walls, acting like natural antibiotics. A group in Japan 9 years ago showed that defensins from animals could inhibit HIV, but the work received little notice.
In their study, the Aaron Diamond researchers teamed up with scientists from Ciphergen Biosystems Inc. in Fremont, California, to compare secretions of CD8 cells--immune cells that play a critical role in battling HIV--from three groups of people. They examined three HIV-infected "long-term nonprogressors," four HIV-infected "progressors," and 15 uninfected people. The team found that only the long-term nonprogressors and uninfected people produced three small, related proteins that a database search revealed as defensins, they report in the 26 September online Science. Furthermore, when Ho and his colleagues depleted the defensins in the cell secretions from the long-term nonprogressors, they found that the secretions had markedly less anti-HIV activity. Ho and Zhang say the shortage of pure defensin material makes it difficult to conduct experiments that might tease out how it combats HIV. But they have now begun those experiments.
The work is "certainly a big advance," says Robert Siliciano, an AIDS virologist at Johns Hopkins University in Baltimore, Maryland. But it's also creating controversy. Although Levy himself applauds "the great effort" to find the defensins in CD8s, he says that it's not the factor he postulated: His lab, he says, tested defensins and found that they did not meet his criteria for CAF.