A TYROSINE-BASED MOTIF IN THE CYTOPLASMIC DOMAIN OF THE ALPHAVIRUS ENVELOPE PROTEIN IS ESSENTIAL FOR BUDDING

The budding of enveloped viruses from cellular membranes is believed t o be dependent on the specific interaction between transmembrane spike proteins and cytoplasmic core components of the virus. We found that the cytoplasmic domain of the E2 transmembrane spike glycoprotein of S emliki Forest virus contains two essential determinants which are abso lutely needed for budding. The first constitutes a single tyrosine res idue in the context of a direct pentapeptide repeat. The tyrosine coul d only partially be substituted for other residues with aromatic or bu lky hydrophobic side chains, although these immediately reverted to th e original genotype. The second determinant involves palmitylated cyst eine residues flanking the tyrosine repeat motif. The function of thes e is probably to anchor the tail against the inner surface of the memb rane so that the tyrosine-containing motif is properly presented to th e nucleocapsid. This is the first example where a membrane virus emplo ys a tyrosine signal for the selective incorporation of spike proteins into budding structures.