icon-folder.gif   Conference Reports for NATAP  
  42nd ICAAC Meeting
San Diego, Sept 27-31, 2002
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New Discovery in HIV
Reported by Jules Levin
  David Ho and the research organization he heads, Aaron Diamond AIDS Research Center in NYC, held a press conference call yesterday which I participated in. He announced identifying a protein discussed below that appears to be the reason why long-term non-progressors appear to progress very slowly. He has not yet identified any therapeutic interventions using this protein & concept but he and his team is working on this. This discovery is in early research stages and hopefull will open the door to additional research in this area by others in addition to Ho. Ho talked about the possibility of this discovery turning into a vaccine or for preventing transmission by sex. But these advancements appear a ways off if they can be developed at all.
Discovery Could Lead to New Approaches to HIV Treatment
New York, NY (September 26, 2002) -In a study published today in Science, researchers from the Aaron Diamond AIDS Research Center (ADARC), an affiliate of The Rockefeller University, announced that they have identified a group of proteins, called alpha-defensins-1, -2, and -3, that can inhibit HIV replication. The discovery, which could have significant implications for the future of HIV treatment, may help explain why some people infected with HIV live significantly longer than others with the virus without developing AIDS.
"This discovery is a major step forward in our understanding of how the body fights HIV," said Dr. Linqi Zhang, the lead scientist of the ADARC research team. "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."
Scientists have known since 1986 that the human body's CD8 T cells can produce unidentified factors capable of inhibiting HIV replication. In particular, the CD8 T cells of a small percentage of people with HIV known as long-term non-progressors can produce high concentrations of these factors, which may help their bodies keep HIV under control despite prolonged infection. Long-term non-progressors make up about 1 to 2% of all people living with HIV in the U.S.
Despite extensive research efforts, the identity of the HIV-fighting factors remained elusive until today's announcement. Research in 1995 found a family of proteins called beta-chemokines that could account for some of the viral suppression in non-progressors, but beta-chemokines were ineffective against many strains of the virus and could not fully explain the non-progressor phenomenon.
The anti-HIV proteins identified in the study published today, alpha-defensin-1, -2, and -3, are active against all strains of the virus. The study findings suggest that the alpha-defensins may have therapeutic applications for people living with HIV.
"Alpha-defensins are promising as a future addition to the HIV treatment arsenal," said Dr. David Ho, Director of ADARC and a co-author of the study. "Researchers from the Aaron Diamond AIDS Research Center are already pursuing new therapeutic approaches based on the data published today."
Researchers evaluated the anti-HIV potency of alpha-defensin-1, -2, and -3 by testing synthetic alpha-defensins as well as purified versions derived from human immune cells. While both versions were active against the virus, tests showed that the purified form was at least 10-20 times stronger than synthetic form. ADARC researchers are currently working to improve the potency of the proteins by genomic and proteomic techniques.
In seeking to isolate and identify the defensins, researchers used a novel, chip-based protein analysis system, called the ProteinChip® Biomarker System, to compare CD8 T-cells from long-term non-progressors with cells from HIV patients whose immune systems had begun to fail. This system, developed by Ciphergen Biosystems, Inc., allowed for the identification and characterization of the defensins much faster and with greater sensitivity than traditional methods allow. Alpha-defensin-1, -2, and -3 were found in all of the patients who remained healthy, but none of the patients whose infections had progressed.
To confirm that these three proteins were responsible for controlling the virus, ADARC researchers artificially stripped the alpha-defensins from proteins made by CD8 T cells taken from long-term non-progressors, and found that their anti-HIV activity was virtually eliminated. From this finding, the scientists concluded that alpha-defensin-1, -2, and -3 are the long-sought immune factors that may help some people with HIV remaining healthy despite being HIV-positive for many years.
About the Aaron Diamond AIDS Research Center
Establish in 1991, the Aaron Diamond AIDS Research Center is the world's largest private research laboratory devoted solely to biomedical research on HIV/AIDS. Under the direction of Dr. David Ho, ADARC has played an important role in research that has helped advance scientific understanding of HIV and improve clinical care for people with HIV/AIDS. ADARC is affiliated with The Rockefeller University.
About Rockefeller University
Founded by John D. Rockefeller in 1901, The Rockefeller University was the nation's first biomedical research university. Today it is internationally renowned for research and graduate education in the biomedical sciences, chemistry, bioinformatics and physics. A total of 21 scientists associated with the university have received the Nobel Prize in medicine and physiology or chemistry, 16 Rockefeller scientists have received Lasker Awards, 5 have been named MacArthur Fellows and 11 have garnered the National Medical of Science. More than a third of the current faculty are elected members of the National Academy of Sciences.