Cholesterol keeps HIV-1 production healthy

To enable the production of progeny HIV particles the Gag protein must attach to the inner surface of the cell membrane, but the exact location of this attachment remains unclear. In November 20 Early Edition Proceedings of the National Academy of Sciences, Akira Ono and Eric Freed from National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, US show that Gag attaches to cholesterol and subsequent HIV-1 particle production requires the presence of cholesterol-enriched microdomains, or 'rafts', in the plasma membrane.

Ono & Freed identified a series of mutations at the C-terminus of the Gag protein and observed that the matrix domain at the N-terminus of the protein was necessary and sufficient for Gag to mediate raft binding (Proc Nat Acad Sci USA 2001, 98:13925-13930).

They then induced raft disruption in HIV-transfected HeLa cells with two classes of cholesterol-depleting drugs. They found that a cyclic sugar compound that extracts ...