POSTASSEMBLY CLEAVAGE OF A RETROVIRAL GLYCOPROTEIN CYTOPLASMIC DOMAINREMOVES A NECESSARY INCORPORATION SIGNAL AND ACTIVATES FUSION ACTIVITY

Viral protease-mediated cleavage within the cytoplasmic domain of the transmembrane (TM) glycoprotein of the type D retrovirus, Mason-Pfizer monkey virus, removes approximately 16 amino acids from the carboxy t erminus of the protein. To determine the functional significance of th is cleavage in the virus life cycle, we introduced premature stop codo ns into the TM coding domain, resulting in the production of truncated glycoproteins. Progressive truncation of the cytoplasmic domain ident ified the carboxy-terminal third as being required for efficient incor poration of the glycoprotein complex into budding virions and profound ly increased the fusogenic capability of the TM glycoprotein. These re sults, together with the ability of matrix protein mutations to suppre ss TM cleavage, imply that this portion of the glycoprotein interacts specifically with the capsid proteins during budding, suppressing glyc oprotein fusion function until virus maturation has occurred.