Benjouad A, Mabrouk K, Gluckman J C, Fenouillet E
Laboratoire de Biologie et Génétique des Pathologies Immunitaires, CNRS URA, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
FEBS Lett. 1994 Mar 21;341(2-3):244-50. doi: 10.1016/0014-5793(94)80465-6.
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.
人类免疫缺陷病毒1型（HIV-1）的gp160包膜糖蛋白是当前疫苗试验的重要组成部分。gp160的聚糖部分高度唾液酸化，已被证明会影响gp160的免疫原性。在此，我们使用一组合成的V3肽，对经去唾液酸化重组gp160LAI免疫的兔子中产生的抗V3抗体进行了表征。V3的GPGR尖端两侧的氨基酸残基对于针对天然或去唾液酸化gp160产生的抗V3抗体的识别是必需的。这两种类型的抗体都与MN和SF2毒株的V3肽以及北美/欧洲V3共有肽发生反应，而抗去唾液酸化gp160LAI抗体除了与CDC4、WMJ2和NY5毒株的V3反应外，还发生反应。然而，通过圆二色性测定，V3肽的二级结构没有显著差异。抗去唾液酸化gp160LAI抗体对V3MN的滴度和亲和力明显低于抗天然gp160LAI抗体，这可能解释了抗去唾液酸化gp160LAI血清无法中和HIV-1MN诱导的合胞体的原因。这些结果表明，V3免疫原性可能受到gp160糖基化模式中细微定向变化的影响。
