IDENTIFICATION OF FUNCTIONAL REGIONS IN THE HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I SU GLYCOPROTEIN

Single conservative and nonconservative amino acid substitutions were introduced into the gp-15 external envelope protein (SU) of human T-ce ll leukemia virus type I (HTLV-I). The mutated amino acids were those identified as being conserved in HTLV-I, HTLV-II, and simian T-cell le ukemia virus type I (but not in bovine leukemia virus). The mutated en velopes were tested for intracellular maturation and for function. Mut ants with three major phenotypes could be defined: (i) 9 mutants with a wild-type phenotype, which included most of the conservative amino a cid changes (five of seven) distributed throughout the SU protein; (ii ) 8 mutants with affected intracellular maturation, 6 of which define a region in the central part of the SU protein essential for correct f olding of the protein; and (iii) 13 mutants with normal intracellular maturation but impaired syncytium formation. These mutations likely af fect the receptor binding step or postbinding events required for fusi on. Five of these mutations are located between amino acids 75 and 101 of the SU protein, in the amino-terminal third of the molecule. The o ther mutations involve positions 170, 181, 195, 197, 208, 233, and 286 , suggesting that two other domains, one central and one carboxy termi nal, are involved in HTLV-I envelope functions.