Amino acid changes at positions 173 and 187 in the human T-cell leukemia virus type 1 surface glycoprotein induce specific neutralizing antibodies

The nucleotide sequence of human T-cell leukemia virus type 1 (HTLV-1) is h ighly conserved, most strains sharing at least 95% sequence identity. This sequence conservation is also found in the viral env gene, which codes for the two envelope glycoproteins that play a major role in the induction of a protective immune response against the virus. However, recent reports have indicated that some variations in env sequences may induce incomplete cros s-reactivity between HTLV-1 strains. To identify the amino acid changes tha t might be involved in the antigenicity of neutralizable epitopes, we const ructed expression vectors coding for the envelope glycoproteins of two HTLV -1 isolates (2060 and 2072) which induced human antibodies with different n eutralization patterns. The amino acid sequences of the envelope glycoprote ins differed at four positions. Vectors coding for chimeric or point-mutate d envelope proteins were derived from 2060 and 2072 HTLV-1 env genes. Syncy tium formation induced by the wild-type or mutated envelope proteins was in hibited by human sera with different neutralizing specificities. We thus id entified two amino acid changes, 1173 --> V and A187 --> T, that play an im portant role in the antigenicity of neutralizable epitopes located in this region of the surface envelope glycoprotein.