A PLASMA-MEMBRANE LOCALIZATION SIGNAL IN THE HIV-1 ENVELOPE CYTOPLASMIC DOMAIN PREVENTS LOCALIZATION AT SITES OF VESICULAR STOMATITIS-VIRUSBUDDING AND INCORPORATION INTO VSV VIRIONS

Previous studies showed that the HIV-I envelope (Env) protein was not incorporated into vesicular stomatitis virus (VSV) virions unless its cytoplasmic tail was replaced with that of the VSV glycoprotein (G). T o determine whether the G tail provided a positive incorporation signa l for Env, or if sequences in the Env tail prevented incorporation, we generated mutants of Env with its 150-amino-acid tail shortened to 29 , 10, or 3 amino acids (Envtr mutants). Cells infected with VSV recomb inants expressing these proteins or an Env-G tail hybrid showed simila r amounts of Env protein at the surface. The Env-G tail hybrid or the Envtr3 mutant were incorporated at the highest levels into budding VSV virions. In contrast, the Envtr29 or Envtr10 mutants were incorporate d poorly. These results defined a signal preventing incorporation with in the 10 membrane-proximal amino acids of the Env tail. Confocal micr oscopy revealed that this signal functioned by causing localization of human immunodeficiency virus type I Env to plasma membrane domains di stinct from the VSV budding sites, where VSV proteins were concentrate d. (C) 1998 Academic Press.