The Year in Science: AIDS 1997

HIV's Harpoon

By Josie Glausiusz|Thursday, January 01, 1998
RELATED TAGS: HIV & AIDS
The AIDS virus has unique and devilish tricks that make it so deadly. But in one respect, researchers reported last April, it is much like the common flu: it uses the same type of harpoon to penetrate a cell and infect it. HIV latches onto an immune cell with the help of a knobby structure. The top of the knob, which binds to a receptor on the cell surface, is a protein called gp120. The base of the knob is made of another protein, gp41. David Chan and his colleagues at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, determined the structure of gp41 by means of X-ray crystallography—by observing how crystals of the protein scatter X-rays.

Each molecule of gp41, they found, contains a spiral region, and in the hiv knob three of these spirals entwine, forming a braidlike structure called a coiled coil. At the top the braid unravels, and the loose ends fall down along the grooves of the coiled coil. When the tip of the knob, gp120, latches onto the immune cell’s receptors, it flips back like the lid on a tin can, releasing the coiled coil within. It’s rather like a harpoon that springs out—a barb that pierces the cell membrane, says Chan’s colleague Peter Kim. The virus then fuses with the cell membrane and dumps its genes inside. Coiled coils have been found in flu viruses, and their use in HIV, which is not related to influenza, makes Chan and Kim suspect this is a common viral ploy.

Before HIV can launch its harpoon, though, it must first attach to cd4, a common receptor on immune cells, as well as to a coreceptor that helps position it properly—and this is where the virus’s unique devilishness becomes more evident. In July molecular immunologist Dan Littman and his colleagues at New York University Medical Center discovered two more coreceptors that HIV can use—one is on immune cells in the lymph nodes and the colon, the other is found only in the colon. That brings the total to six, which makes hiv exceptionally flexible. Trying to block one of these receptors, as some researchers have suggested, may therefore be a dubious approach to therapy. If you develop a drug that blocks one receptor, the virus might mutate itself, says Littman, so you’ll accumulate virus that can use another coreceptor and do just as much harm or maybe more.
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