Effect of sialic acid removal on the antibody response to the third variable domain of human immunodeficiency virus type-1 envelope glycoprotein.
The gp160 envelope glycoprotein of human immunodeficiency virus type-1 (HIV-1) is an essential component of current vaccine trials. The glycans of gp160, part of which are highly sialylated, have been shown to influence gp160 immunogenicity. Here, using a panel of synthetic V3 peptides, we characterized the anti-V3 antibodies generated in rabbits immunized by desialylated recombinant gp160LAI. Amino acid residues flanking the GPGR tip of V3 were necessary for the recognition by anti-V3 antibodies raised against either the native or desialylated gp160. Both types of antibodies reacted to V3 peptides of MN and SF2 strains and with a North American/European V3 consensus peptide, while anti-desialylated gp160LAI antibodies reacted in addition to the V3 of CDC4, WMJ2 and NY5 strains. Yet, the V3 peptides did not significantly differ in their secondary structure, as determined by circular dichroism. The titer and avidity for V3MN of anti-desialylated gp160LAI antibodies were significantly lower than those of anti-native gp160LAI, which likely accounts for the inability of anti-desialylated gp160LAI sera to neutralize HIV-1MN-induced syncytia. These results indicate that V3 immunogenicity may be influenced by subtle directed changes in the gp160 glycosylation pattern.
Benjouad
A
A
Laboratoire de Biologie et Génétique des Pathologies Immunitaires, CNRS URA, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Mabrouk
K
K
Gluckman
J C
JC
Fenouillet
E
E
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D002942:Circular Dichroism; D003429:Cross Reactions; D015686:Gene Products, env / Q000737:chemistry / Q000276:immunology*; D015726:Giant Cells; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology*; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D010449:Peptide Mapping; D010455:Peptides / Q000276:immunology; D011498:Protein Precursors / Q000737:chemistry / Q000276:immunology*; D011817:Rabbits; D017386:Sequence Homology, Amino Acid; D012794:Sialic Acids / Q000276:immunology*
D000914:Antibodies, Viral; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D012794:Sialic Acids; D019158:N-Acetylneuraminic Acid