Intracellular Trafficking of HIV-1 Gag: How Gag Interacts with Cell Membranes and Makes Viral Particles
Marilyn D. Resh
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*Correspondence: Marilyn D. Resh, Email not available
Abstract
The Gag polyprotein of retroviruses and lentiviruses is the master orchestrator of viral particle formation.HIV-1 Gag is synthesized on cytosolic polysomes where it is co-translationally modified withthe 14-carbon fatty acid myristate. New findings shed light on how myristoylated HIV-1 Gag trafficsthrough the cell, binds to specific membranes, and assembles into virions. The affinity of Gag formembrane bilayers is regulated by a myristoyl switch; Gag multimerization induces the fatty acid toflip away from the protein, thereby promoting membrane binding during assembly. Several recentstudies have shown that newly synthesized Gag traffics first to multivesicular bodies (MVB), endosomalcompartments that contain protein complexes necessary for particle budding. Signals withinGag, as well as specific host-cell lipids and proteins, promote MVB localization. In macrophages, Gagis retained in MVBs; viral particles are formed within the MVB lumen and released from the cell viaexocytosis. In other cell types, Gag and/or MVBs rapidly transit to the plasma membrane whereparticle release occurs. Given that MVB exocytosis is an essential host-cell pathway, effective antiviralagents will need to specifically target interaction of Gag with the endocytic pathway withoutperturbing the normal host-cell trafficking network.
