Neutralization of HIV-1: A Summary
The pressing need to devise a vaccine against HIV-1 fuels an intensive and ongoing study of its neutralization. The envelope protein has been sequenced and a structure computed (Ratner et al. 1985; Modrow et al. 1987; Leonard et al. 1990) but understanding of functional relationships awaits its crystallization and determination of its atomic structure (see reviews by McKeating and Willey 1989; Putney and McKeating 1990). The envelope protein is heavily glycosylated (about 50% of its mass is carbohydrate) and is post-translationally cleaved into the anchor, gp41, and a non-covalently linked distal segment gp120. Two or four of these units form the mature spike protein (Thomas et al. 1991) and there are 70–80 spikes per virion (Gelderblom et al. 1987). By comparing amino acid sequences of seven different strains, Modrow et al. (1987) identified five variable (V) and six constant (C) regions interspersed throughout gp120 and gp41. These and some information relevant to neutralization are shown in Figs. 2 and 10. The use of synthetic peptides to elicit or identify reactive antibody has located 12 possible antigenic sites, ten of which are neutralizing, although some of these are probably part of the same discontinuous site (Table 14; Fig. 10). Nonneutralization sites are also known on gp120 and gp41 (e.g. Banapour et al. 1987; Lasky et al. 1987; Linsley et al. 1988; Kinney-Thomas et al. 1988; Ardman et al. 1990; Larcher et al. 1990; Teeuwsen et al. 1990; Robinson et al. 1991; Xu et al. 1991) and include epitopes on the neutralization immunodominant V3 loop (Langedijk et al. 1991 ; Laman et al. 1992). Attention in regard to neutralization has concentrated on the V3 loop (Fig. 2b) which is concerned with the entry process and, in particular, the fusion of viral and cellular membranes.
KeywordsEnvelope Protein Attachment Site Antigenic Site Compare Amino Acid Sequence Neutralization Site
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