GLYCOPROTEIN INCORPORATION AND HIV-1 INFECTIVITY DESPITE EXCHANGE OF THE GP160 MEMBRANE-SPANNING DOMAIN

We have examined the role of the membrane-anchoring domain of the HIV- 1 glycoproteins in viral glycoprotein function, glycoprotein incorpora tion, and viral infectivity. For this purpose, we initially exchanged the entire membrane-spanning region with that from a cellular glycopro tein (CD22). Subsequently, the strictly conserved arginine in the cent ral position of the transmembranal alpha-helix was replaced by a neutr al residue (R(696) --> I-696). We have further examined the requiremen ts within the cytoplasmic C-terminus for glycoprotein incorporation an d replaced this region of gp160 with the long cytoplasmic C-terminus ( 118 amino acids) from CD22. Our results show that the specific amino a cid sequence of the membrane-spanning region of gp160 is not necessary for viral infectivity, thus making it unlikely that this region is sp ecifically involved in membrane fusion, in glycoprotein incorporation, or in infectivity of the cell lines tested. In contrast, recombinant gp160 with the CD22 C-terminal region, although present at the cell su rface and membrane fusion-competent, was excluded from incorporation i nto particles. This could indicate that steric exclusion, and no pseud otyping, occurs when the heterologous, cytoplasmic C-terminal region i s too long and not fitting. (C) 1996 Academic Press, Inc.