Productive human immunodeficiency virus type 1 assembly takes place at the plasma membrane

J Virol. 2007 Jul;81(14):7476-90. doi: 10.1128/JVI.00308-07. Epub 2007 May 16.

Abstract

Gag proteins are necessary and sufficient to direct human immunodeficiency virus type 1 (HIV-1) particle assembly and budding. Recent evidence suggests that Gag targeting to late endosomal/multivesicular body (LE/MVB) compartments occurs prior to viral particle budding at the plasma membrane (PM). However, the route that Gag follows before reaching its steady-state destinations still remains a subject of debate. Using a subcellular fractionation method that separates PM from LE/MVB combined with pulse-chase labeling, we analyzed Gag trafficking in HIV-1-producing HEK 293T cells. Our results reveal that the majority of newly synthesized Gag is primarily targeted to the PM. While PM-targeted Gag was efficiently released, a significant fraction of the remaining cell surface-associated Gag was found to be subsequently internalized to LE/MVB, where it accumulated, thus accounting for the majority of LE/MVB-associated Gag. Importantly, this accumulation of Gag in LE/MVB was found to be cholesterol dependent since it was sensitive to the sterol-binding drugs filipin and methyl-beta-cyclodextrin. These results point towards the PM as being the primary site of productive HIV-1 assembly in cells that also support Gag accumulation in intracellular compartments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Compartmentation
  • Cell Line
  • Cell Membrane / virology*
  • Endocytosis
  • Gene Products, gag / metabolism
  • HIV-1 / metabolism
  • HIV-1 / physiology*
  • Humans
  • Microscopy, Electron, Transmission
  • Protein Transport
  • Subcellular Fractions / metabolism
  • Virus Assembly*

Substances

  • Gene Products, gag