Sequence variations in the amino- and carboxy-terminal parts of the surface envelope glycoprotein of HTLV type 1 induce specific neutralizing antibodies.
The surface envelope glycoprotein gp46 of the human T cell leukemia virus type 1 elicits a strong immune response. Its protective role against HTLV-1 infection in animal models is well established, suggesting that recombinant envelope glycoproteins or synthetic peptides could be used as an effective vaccine. However, reports have indicated that some variations in envelope sequences may induce incomplete cross-neutralization between HTLV-1 strains. To identify amino acid changes that might be involved in induction of specific neutralizing antibodies, we studied sera from three patients (2085, 2555, and 2709) infected by HTLV-1 with surface glycoprotein gp46 harboring variations in amino acid sequence at positions 39, 72, 265, and 290. Inhibition of syncytia induced by parental, chimeric, or point-mutated envelope proteins indicated that sera 2555 and 2709 primarily recognized neutralizable epitopes located in N- and C-terminal parts of the gp46 glycoprotein. Amino acids changes at positions 39, 265, and 290 greatly impaired recognition of neutralizing epitopes recognized by these two sera. These results demonstrate that amino acid changes in envelope glycoprotein gp46 can induce strain-specific neutralizing antibodies in some patients. On the other hand, the neutralizing activity of serum 2085 was not affected by amino acid changes at positions 39, 265, and 290, suggesting that the neutralizing antibodies present in this serum were directed against epitopes located in other parts of the molecule, possibly those located in the central domain of the molecule, which has the same amino acid sequence in the three viruses.
Tallet
B
B
Laboratoire de Virologie and CNRS-UMR5097, Université Victor Ségalen Bordeaux 2, 33076 Bordeaux cedex, France.
Astier-Gin
T
T
Moynet
D
D
Londos-Gagliardi
D
D
Guillemain
B
B
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D015686:Gene Products, env / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D014644:Genetic Variation / Q000235:genetics*; D015726:Giant Cells / Q000502:physiology; D015481:HTLV-I Antibodies / Q000097:blood* / Q000276:immunology; D015486:HTLV-I Antigens / Q000276:immunology; D015490:HTLV-I Infections / Q000276:immunology / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D014162:Transfection
D015686:Gene Products, env; D015481:HTLV-I Antibodies; D015486:HTLV-I Antigens; D011993:Recombinant Fusion Proteins; D015682:Retroviridae Proteins, Oncogenic; C055266:gp46 protein, Human T-cell leukemia virus type I