HIV Needs Cholesterol to Invade Cells; Cholesterol-Lowering Drugs Could Block HIV Replication
HIV must attach to " cholesterol-rich" patches within a cell's membrane to invade a cell and reproduce, raising the possibility of fighting HIV with cholesterol-lowering drugs, according to a study conducted by National Institute of Allergy and Infectious Disease researchers that appears in today's Proceedings of the National Academy of Sciences. "Our research raises the intriguing possibility that widely used cholesterol-lowering drugs might have an effect in humans similar to what we have found in these initial laboratory studies," lead author Dr. Eric Freed of NIAID's Laboratory of Molecular Biology said. Freed and his colleagues set out to prove that an HIV protein called "Gag" needed cholesterol to attach to the inner surface of the immune cells that HIV targets. Animal cells have a double-walled outer membrane that is made up of fluid and some relatively solid parts, including small cholesterol-filled patches called "rafts." In the immune cells, these rafts are most concentrated at places where cells meet.
Lower Cholesterol, Fight HIV
Freed and co-author Dr. Akira Ono first confirmed that Gag attaches to the rafts and then created several "mutant" forms of the protein that helped them discover that two pieces of the protein are necessary for HIV to successfully attach to the cholesterol rafts. Using two different compounds, the researchers either removed cholesterol from the rafts or disrupted cholesterol synthesis. Used alone, each compound significantly reduced HIV's ability to replicate and infect new cells. Used together, HIV replication was "almost completely abolished" (NIH release, 11/19). "Additional experiments are needed to determine whether this interaction can be interrupted therapeutically to treat HIV-infected people," Freed said (Agence France-Presse, 11/20). The compounds have not yet been tested in humans (BBC News, 11/20). Freed added that the compounds could eventually lead to new drugs to fight HIV (AP/Contra Costa Times, 11/20).