Study: AIDS Virus Seeks Cholesterol

Researchers at the National Institute of Allergy and Infectious Diseases have found an important role for cholesterol in how HIV infects a cell. Long known as the conveyor of HIV, a protein known as Gag seeks a place on a cell's membrane that is rich in cholesterol.

In laboratory studies, researchers Eric O. Freed, Ph.D. and Akira Ono, Ph.D. found that when they removed cholesterol from the cells targeted by HIV, the virus' ability to make new viral particles, and thus to replicate, was inhibited. The cells targeted by HIV are known as rafts, and they are the sites where HIV attaches to the inner cell membrane surface. The findings give a much more detailed picture of how HIV travels into and out of cells, as well as possible ways to block that travel.

Rafts are believed to be most concentrated at points of cell-to-cell contact in the immune cells that HIV targets. Any mechanism that helps HIV find and attach to rafts would help the virus spread. Conversely, even a modest degree of disruption could slow the virus' spread because it would hinder the virus' ability to enter and leave its host cells.

Freed and Ono first established that Gag does indeed attach to rafts. They then created several mutant forms of Gag and learned that two pieces of the protein are required for attachment. Finally, the authors turned to the question of what happens if HIV is kept on the rafts, unable to enter the cell membrane.

To determine the answer, the investigators depleted cholesterol from rafts in two ways. Using two compounds, one that removes cholesterol rapidly from the cell surface and one that inhibits cholesterol synthesis, the authors found that each method significantly reduced HIV's ability to form particles that could infect new cells. Applied together to virus-producing cells, the compounds completely abolished HIV's power to replicate.

The study is published in the November 20, 2001 issue of the Proceedings of the National Academy of Sciences ("Plasma Membrane Rafts Play a Critical Role in HIV-1 Assembly and Release," Vol. 98:13925-13930).

Back to other CDC news for November 21, 2001

Previous Updates