2 NEUTRALIZING DOMAINS IN THE V3 REGION IN THE ENVELOPE GLYCOPROTEIN GP125 OF HIV TYPE-2

The purposes of this study were to map the targets for neutralizing Ab s in the HIV-2 glycoproteins with particular emphasis on the role of t he V3 region. Sera obtained from guinea pig immunized with peptides re presenting five immunogenic regions of the envelope proteins were used in cross-neutralization experiments with nine HIV-2 isolates. Broad c ross-neutralizing activity was elicited by immunization with two pepti des representing the central and COOH-terminal portions of the HIV-2 V 3 loop. Murine mAbs were established from animals immunized with two c orresponding overlapping peptides. Six mAbs showed neutralizing activi ty against the homologous virus isolate SBL-6669. Peptide absorption e xperiments were performed to define the target regions for human neutr alizing Abs in the HIV-2 envelope glycoproteins. A significant blockin g of neutralizing activity of five HIV-2 Ab-positive sera was seen in the presence of two peptides corresponding to the V3 region. Two overl apping deletion sets of peptides, representing amino acids Ser(311) an d Arg(337), were used to identify the role of individual HIV-2 V3 amin o acids in the binding of polyclonal and mAbs. Two distinct antigenic sites were identified in this region, the first corresponding to a reg ion including the conserved motif Phe-His-Ser (amino acid 315-317) and the second in proximity of the COOH-terminal cysteine Trp-Cys-Arg (am ino acid 329-331). Potentially these two sites can interact to represe nt a single discontinuous antigenic site. Taken together, these result s indicate that V3 is an important neutralizing domain of HIV-2.