Abstract
The incorporation of the envelope glycoprotein complex (Env) onto the developing particle is a crucial step in the HIV-1 lifecycle. The long cytoplasmic tail (CT) of Env is required for the incorporation of Env onto HIV particles in T cells and macrophages. Here we identify the Rab11a-FIP1C/RCP protein as an essential cofactor for HIV-1 Env incorporation onto particles in relevant human cells. Depletion of FIP1C reduced Env incorporation in a cytoplasmic tail-dependent manner, and was rescued by replenishment of FIP1C. FIP1C was redistributed out of the endosomal recycling complex to the plasma membrane by wild type Env protein but not by CT-truncated Env. Rab14 was required for HIV-1 Env incorporation, and FIP1C mutants incapable of binding Rab14 failed to rescue Env incorporation. Expression of FIP1C and Rab14 led to an enhancement of Env incorporation, indicating that these trafficking factors are normally limiting for CT-dependent Env incorporation onto particles. These findings support a model for HIV-1 Env incorporation in which specific targeting to the particle assembly microdomain on the plasma membrane is mediated by FIP1C and Rab14.
Highlights
HIV-1 particles assemble on the plasma membrane of infected human cells
The limited number of envelope glycoprotein complex (Env) trimers on HIV-1 particles suggested to us that there is an inherent limitation to Env incorporation that is unrelated to the production of Env protein in the cell
HIV-1 Env itself is quite selective in its ability to pseudotype other retrovirus particles
Summary
HIV-1 particles assemble on the plasma membrane of infected human cells. The underlying shell of the developing viral particle is formed by the Pr55Gag polyprotein (Gag), which is translated deep within the cytoplasm of cells and reaches the plasma membrane by an unknown mechanism [1,2,3]. Gag binds to the viral genomic RNA through its nucleocapsid (NC) region and is responsible for packaging of RNA into the developing particle. Gag-Pol, and the associated viral genomic RNA traffic together to the particle assembly site on the plasma membrane. The envelope glycoprotein complex (Env) of HIV-1 is simultaneously incorporated onto the lipid membrane of the developing particle, and yet must travel via a very different route to reach the assembly site
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