Serendipity Bridges Gap Between Research On HIV Receptors And Antibodies

April 01, 1997

Philadelphia, Pa. -- The big news from the HIV basic research front in 1996 was the discovery by Penn researchers and others of a group of cell-surface receptor molecules that, along with the long-known receptor CD4, must be present for the virus to enter and infect cells of the immune system. The usual role of these receptors is to offer binding sites for various chemokines, a family of molecules involved in mediating immune responses; different HIV strains, however, have evolved to use the receptors for their purposes, too.

During the same period, James A. Hoxie, MD, an associate professor of medicine, and his coworkers developed an antibody against one of these important chemokine receptors, a molecule called CXCR4, or fusin, discovered at the National Institutes of Health -- although this fact was not immediately apparent to them.

The Penn scientists had originally set out to produce monoclonal antibodies to SIV, or simian immunodeficiency virus, which causes an AIDS-like disease in monkeys. To do this, they immunized mice with SIV-infected cells and screened antibodies derived from the mice for the ability to block infection by the virus in cell lines. While they were successful in producing a number of antibodies against SIV in this way, they also inadvertently stumbled upon an antibody that was able to block infection but that reacted with the cell rather than with the virus. When this antibody, termed 12G5, was also shown to block some types of HIV from infecting cells, they redoubled their efforts to identify the molecule with which 12G5 was reacting. Following the lead that CXCR4 was required by some viruses to infect cells, they checked to see if 12G5 reacted with CXCR4 and were pleasantly surprised to find that it did.

The new antibody represented the first anti-CXCR4 antibody and has since made many new studies involving this molecule possible. As a tool, the antibody has enormous value to HIV investigators, as evidenced by the fact that Hoxie has so far supplied it on request to about 250 other laboratories around the world.

"Our discovery of this antibody was somewhat serendipitous, but now we're up and running with a unique reagent that has been extremely useful to many laboratories" says Hoxie. In the March 4 issue of the Proceedings of the National Academy of Sciences, for example, researchers at Harvard Medical School and LeukoSite Inc. used Hoxie's antibody and one against another chemokine receptor known as CCR5 to create a detailed hypothesis describing how HIV infection leads to the slow, progressive destruction of the immune system.

-- Dr. James A. Hoxie can be reached at (215) 898-0261.

The University of Pennsylvania Medical Center's sponsored research ranks fifth in the United States, based on grant support from the National Institutes of Health, the primary funder of biomedical research in the nation -- $149 million in federal fiscal year 1996. In addition, for the second consecutive year, the institution posted the highest growth rate in its research activity -- 9.1 percent -- of the top ten U.S. academic medical centers during the same period. Penn news releases are available to reporters by direct e-mail, fax, or U.S. mail, upon request. They are also posted electronically to EurekAlert! (http://www.eurekalert.org), an Internet resource sponsored by the American Association for the Advancement of Science, and to the SciNews-MedNews section of the Journalism Forum, a component of CompuServe. Additionally, they are distributed via the electronic news service Quadnet. [hoxie.rel]
-end-


University of Pennsylvania School of Medicine

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