Association of structural changes in the V2 and V3 loops of the gp120 envelope glycoprotein with acquisition of neutralization resistance in a simian-human immunodeficiency virus passaged in vivo

The in vivo passage of a neutralization-sensitive, laboratory-adapted simia n-human immunodeficiency virus (SHIV-HXBc2) generated a pathogenic, neutral ization-resistant virus, SHIV-HXBc2P 3.2. SHIV-HXBc2P 3.2 differs from SHIV -HXBc2 only in 13 amino acid residues of the viral envelope glycoproteins. Here we used antibody competition analysis to examine the structural change s that occurred in the SHIV-HXBc2P 3.2 gp120 exterior envelope glycoprotein . The relationships among the antibody epitopes on the conserved gp120 core of SHIV-HXBc2 and SHIV-HXBc2P 3.2 were similar. The third variable (V3) lo op was more closely associated with the fourth conserved (C4) region and CD 4-induced epitopes on the gp120 core in the HXBc2P 3.2 gp120 glycoprotein c ompared with the HXBc2 gp120 glycoprotein. Rearrangements of the second var iable (V2) loop with respect to the CD4 binding site and associated epitope s were evident in comparisons of the two gp120 glycoproteins. Thus, the in vivo evolution of a neutralization-resistant virus involves conformational adjustments of the V2 and V3 variable loops with respect to the conserved r eceptor-binding regions of the gp120 core.