Important note: Information in this article was accurate in 2002. The state of the art may have changed since the publication date.
Newsday - September 27, 2002
Laurie Garrett, Staff Writer
Scientists at the Aaron Diamond AIDS Research Center in Manhattan may have found a long-sought, mysterious factor secreted by HIV-infected individuals who survive, disease-free, for more than 20 years.
In today's Science magazine, Dr. David Ho and his colleagues announce they have used a new technology to solve the mystery - a finding that has the potential to develop treatments.
But the Ho announcement was greeted with skepticism by some key players in HIV research, one of whom said he tried the same experiments without getting the same results.
For 16 years AIDS researchers have known that some elusive protein - or group of proteins - produced by white blood cells could suppress HIV.
In 1986 Dr. Jay Levy of the University of California in San Francisco discovered that HIV-infected patients who remained healthy for more than a decade had unique immune responses. Most people who become infected mount what is called a CD4 T-cell response, producing millions of the virus-eating cells. But HIV adapts to latch on to a marker on the outside of those cells, ultimately turning them into HIV-production factories.
The immune systems in long-surviving patients, Levy found, were attacking HIV using other immune cells, known as CD8 cells. He demonstrated that CD8 cells secrete a fluid that prevents HIV from manufacturing copies of itself. The exact chemical in the fluid defied attempts to be removed, and Levy dubbed the fluid itself CAF, for "CD8 antiviral factor."
Ho's researchers have studied the CAF from three men who have been HIV positive for more than 24 years and who have yet to develop signs of the disease.
They used a new chip system developed by Ciphergen Biosystems of Fremont, Calif., to find protein needles in proverbial haystacks by vaporizing a liquid sample and ionizing the individual components. A computer reads the ionized samples as they pass spectrographic detectors, comparing them instantly to known proteins.
Three proteins jumped out of the system analysis, Ho said: alpha-defensins 1, 2 and 3, normally found in neutrophil cells, whose task is to gobble up bacteria.
Ho's group used the three defensins against HIV in test tube studies and, he said, the virus was stopped dead in its tracks.
But Levy begs to differ. He said he has tried the technology without the same results.
"CD8 cells are not supposed to make defensins," Levy insisted. " ... Defensins have never come up as made by CD8 cells."
Dr. Bruce Walker of Harvard Medical School said he also is skeptical, though he applauded the Ho experiment.
"The data look reasonable for this. The protein data are elegant, and it appears that small amounts are made by CD8 cells," Walker said. But he characterized the antiviral effect as modest.
"I think there is a worry that the results in larger numbers of patients might be different," he said.
Walker questioned whether CAF will prove as effective as responses that involve so-called acquired immunity - the kind that is "learned" by exposure to disease agents either through vaccination or previous infection.
Ho insisted his critics have not given the results sufficient scrutiny.
"The next step is to figure out the mechanism" of how defensins block HIV, he said. "And for us going forward, it's about how do you improve on the potency of the compounds. Looking forward beyond that, we want to see if there is any clinical utility to defensins, as a therapeutic tool to have in our arsenal."
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