A tyrosine-based motif in the HIV-1 envelope glycoprotein tail mediates cell-type– and Rab11-FIP1C–dependent incorporation into virions

Abstract

Lentiviruses such as HIV-1 encode envelope glycoproteins (Env) with long cytoplasmic tails (CTs) that include motifs mediating interactions with host-cell–trafficking factors. We demonstrated recently that Rab11-family interacting protein 1C (FIP1C) is required for CT-dependent incorporation of Env into HIV-1 particles. Here, we used viruses bearing targeted substitutions within CT to map the FIP1C-dependent incorporation of Env. We identified YW795as a critical motif mediating cell-type–dependent Env incorporation. Disruption of YW795reproduced the cell-type–dependent particle incorporation of Env that had previously been observed with large truncations of CT. A revertant virus bearing a single amino acid change near the C terminus of CT restored wild-type levels of Env incorporation, Gag–Env colocalization on the plasma membrane, and viral replication. These findings highlight the importance of YW795in the cell-type–dependent incorporation of Env and support a model of HIV assembly in which FIP1C/RCP mediates Env trafficking to the particle assembly site.