The transmembrane subunit (TM) of the
avian leukosis and
sarcoma virus (ALSV) envelope
glycoprotein (Env) contains a stretch of conserved hydrophobic
amino acids internal to its amino terminus (residues 21 to 42). By analogy with similar sequences in other
viral envelope glycoproteins, this region has been proposed to be a fusion
peptide. We investigated the role of this region by changing each of three hydrophobic residues (Ile-21, Val-30, and Ile-39) to glutamatic
acid and
lysine in the ALSV subgroup A Env. Like wild-type (wt) Env, all six mutant Env
proteins were proteolytically processed, oligomerized, and expressed at the cell surface in a form that bound Tva, the ALSV subgroup A receptor. Like wt Env, Ile21Glu, Ile21Lys, Va30Glu, and Val30Lys changed conformation upon binding Tva, as assayed by sensitivity to
thermolysin. Ile39Glu and Ile39Lys were cleaved by
thermolysin in both the absence and presence of Tva. Although incorporated into virus particles at approximately equal levels, all mutant Envs were compromised in their ability to support
infection. The mutants at residues 21 and 30 showed levels of
infection 2 to 3 orders of magnitude lower than that of wt Env. The mutants at residue 39 were noninfectious. Furthermore, none of the mutants displayed activity in a cell-cell fusion assay. Our results support the contention that residues 21 to 42 of ALSV subgroup A Env constitute its fusion
peptide.