The nature of the site in the human body that permits the AIDS virus to enter and begin its destruction has been revealed in detail by two independent research teams led by scientists from the Howard Hughes Medical Institute in Bethesda.
Their work, published in today's issue of the journal, Nature, unravels some of the mystery that surrounds the AIDS virus' target and paves the way for the development of new drugs to prevent the human immunodeficiency virus from gaining access to the site, known as CD4.
Denied access to its target, the HIV virus would be harmless.
"We still don't fully understand the interaction between CD4 and HIV," said Wayne Hendrickson, a Hughes researcher and team leader from Columbia University in New York.
CD4 is a protein that protrudes from the surface of T cells, which are found throughout the human body and play a vital role in protecting against infections. A second protein, gp120, sits on the surface of the AIDS virus. Both get into the bloodstream. When they come in contact, they lock to one another.
Through this connection, the AIDS virus gains entry to the T cells. Once that happens, the virus takes command of the cells' chemical machinery and begins to manufacture new copies of the virus. They then are released into the bloodstream, where they attack other T cells.
Eventually, the T cells are reduced to such a low level they cannot fight off to so-called "opportunistic" or overwhelming infections. Some of these, such as pneumonia, can be fatal for AIDS patients.
Working separately, Hendrickson's group and a team headed by another Hughes researcher, Stephen Harrison of Harvard University in Cambridge, Mass., used a series of complex techniques and painstakingly reconstructed three-dimensional images of the crystals.
The images uncover the region on the surface of the CD4 where the AIDS virus binds, said Frank Baldwin, a spokesman for the Hughes Institute.
CD4, first cloned in 1985, has been the subject of intense interest as a possible AIDS therapy.
One approach being tested in clinical trials is to saturate the bloodstream of AIDS patients with a modified form of CD4 in the hope it will serve as a decoy and attach to the virus. Once the AIDS virus is "plugged up" with soluble CD4, it would become harmless since it would not reach the natural CD4 on the T cells.
That proved effective in laboratory cultures but early results from clinical trials have been disappointing. So far, the "decoy" strategy has failed to reduce significantly the amount of virus in patients taking part in the trials.