Researchers may have identified the molecular mechanism that enables HIV to cast its infectious net beyond those cells bearing the CD4 receptor, the loading dock that HIV normally first engages on a cell's surface.

The finding was presented earlier this week (February 1) at the Sixth Conference on Retroviruses and Opportunistic Infections in Chicago, by scientists from the Gladstone Institute of Virology and Immunology at UC San Francisco.

In their study, the investigators discovered that cells bearing the CD4 receptor sometimes interact with neighboring cells that lack the CD4 receptor but do bear a "co-receptor," or secondary loading site, such as CCR5 or CXCR4. Together, these proteins create a receptor complex that HIV recognizes as a single unit.

"This so-called `trans' mechanism expands the range of potential cellular targets for HIV-1," said the senior author of the study, Mark A. Goldsmith, MD, PhD, UCSF assistant professor of medicine at the Gladstone Institute.

It also suggests a possible new focus for drug therapies aimed at preventing the spread of HIV to non-CD4 receptor cells. "We still need to demonstrate this in rodent models," said Goldsmith, "but this is an intriguing start." HIV generally infects the immune system's T-cells, which reside in the blood, latching first onto the CD4 receptor and then onto the CCR5 co-receptor located on the same cell's surface. The multi-step binding process culminates with HIV's fusion with the cell.

However, the virus also migrates from the blood into tissues, infecting various types of cells in the brain, colon, testes, ovaries and heart. Some of these cells are immune system cells, some are not. Many are CD4-negative cells, such as cell's bearing CD8 receptors in lymphoid tissues; astrocytes and endothelial cells in the brain; epithelial cells in the colon; and myocytes in heart tissue.

While CD4-negative cells are not the principle target of HIV infection, studies indicate that th
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Contact: Jennifer O'Brien
jobrien@itsa.ucsf.edu
415-476-2557
University of California - San Francisco
5-Feb-1999