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 highly 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 cross-reactivity between HTLV-1 strains. To identify the amino acid changes that might be involved in the antigenicity of neutralizable epitopes, we constructed expression vectors coding for the envelope glycoproteins of two HTLV-1 isolates (2060 and 2072) which induced human antibodies with different neutralization patterns. The amino acid sequences of the envelope glycoproteins differed at four positions. Vectors coding for chimeric or point-mutated envelope proteins were derived from 2060 and 2072 HTLV-1 env genes. Syncytium formation induced by the wild-type or mutated envelope proteins was inhibited by human sera with different neutralizing specificities. We thus identified two amino acid changes, I173-->V and A187-->T, that play an important role in the antigenicity of neutralizable epitopes located in this region of the surface envelope glycoprotein.
Blanchard
S
S
EP630 CNRS-Université Victor Ségalen Bordeaux 2, 33077 Bordeaux Cedex, France.
Astier-Gin
T
T
Tallet
B
B
Moynet
D
D
Londos-Gagliardi
D
D
Guillemain
B
B
D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D015752:Genes, env / Q000235:genetics; D015726:Giant Cells / Q000502:physiology; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D009500:Neutralization Tests; D017354:Point Mutation; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014162:Transfection; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D006023:Glycoproteins; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins