Open AccessMyristoylation as a target for inhibiting HIV assembly: Unsaturated fatty acids block viral budding
Author(s) -
O. Wolf Lindwasser,
Marilyn D. Resh
Publication year - 2002
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.212409999
Subject(s) - myristoylation , myristic acid , fatty acid , membrane , biochemistry , chemistry , covalent bond , intracellular , cell , cell membrane , budding , microbiology and biotechnology , biology , palmitic acid , organic chemistry
Modification of HIV-1 Gag with myristic acid, a saturated 14-carbon fatty acid (14:0), is essential for HIV-1 assembly. We recently showed that exogenous treatment of cells with unsaturated 14-carbon fatty acids, 5-cis-tetradecenoic acid (14:1n-9) and 5-cis,8-cis-tetradecadienoic acid (14:2n-6), reduces the affinity of some myristoylated proteins for plasma membrane rafts, membrane subdomains that have been shown to be required for efficient assembly of HIV. Here we demonstrate that treatment of cells with 14:1n-9 and 14:2n-6 fatty acids reduced the affinity of Gag for rafts but not membranes in general. Furthermore, treatment of cells with 14-carbon unsaturated fatty acids inhibited Gag-driven particle assembly. These effects most likely reflect covalent modification of Gag with unsaturated fatty acids. Treatment with 14:1n-9 and 14:2n-6 fatty acids did not alter intracellular protein trafficking, nor did it reduce cell viability. These studies suggest a strategy to attack HIV assembly by selectively altering the patterns of fatty acid modification.