While trying to understand how a natural HIV inhibitor works, scientists have discovered that a protein on immune cells promotes HIV infection. Ma and colleagues, reporting in the November 15 issue of The Journal of Experimental Medicine, say that this insight could lead to new approaches for inhibiting infection as HIV enters the body.

Nearly a decade ago, this group of NIH scientists, led by Sharon Wahl, discovered that SLPI, a protein-chopping inhibitor in saliva, could stop HIV from infecting immune cells called macrophages. They knew that SLPI was binding to the cell and not to the virus, but they had no idea how it worked. Their search for SLPI's binding partner on macrophages - and with it a clue to the mechanism of virus inhibition - has now uncovered annexin 2. This protein is known to be involved in shuttling materials into and out of cells but was not previously associated with HIV.

The authors show that HIV infection could be prevented by directly blocking annexin 2 or by eliminating it from the cell surface. Although they do not know exactly how annexin 2 helps HIV get into the cell, Wahl's group now shows that a surface component on HIV that is picked up from infected cells as the virus exits binds annexin 2 and facilitates infection.

In macrophages that lack annexin 2 or are treated with SLPI to block annexin 2, the virus can still attach to the cell, but it hits a roadblock before it can begin to replicate itself. The block probably occurs, according to Wahl, at the membrane-fusion step that is required for the virus to deliver its genetic material into the cell. While more studies need to be done on other cell types, Wahl hopes that SLPI may eventually provide a way to inhibit infection as the virus enters the body.

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Contact: Nickey Henry
henryn@rockefeller.edu
212-327-8366
Journal of Experimental Medicine
15-Nov-2004

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