Variable-loop-deleted variants of the human immunodeficiency virus type 1 envelope glycoprotein can be stabilized by an intermolecular disulfide bondbetween the gp120 and gp41 subunits

We have described an oligomeric gp140 envelope glycoprotein from human immu nodeficiency virus type 1 that is stabilized by an intermolecular disulfide bond between gp120 and the gp41 ectodomain, termed SOS gp120 (J. M. Binley , R. W. Sanders, B. Clas, N. Schuelke, A. Master, Y. Guo, F. Kajumo, D. J. Anselma, P. J. Maddon, W. C. Olson, and J. P. Moore, J. Virol. 74:627-643, 2000). In this protein, the protease cleavage site between gp120 and gp140 is fully utilized. Here we report the characterization of gp140 variants th at have deletions in the first, second, and/or third variable loop (V1, V2, and V3 loops). The SOS disulfide bond formed efficiently in gp140s contain ing a single loop deletion or a combination deletion of the VI and V2 loops . However, deletion of all three variable loops prevented formation of the SOS disulfide bond. Some variable loop-deleted gp140s were not fully proces sed to their gp120 and gp41 constituents even when the furin protease was c otransfected. The exposure of the gp120-gp41 cleavage site is probably affe cted in these proteins, even though the disabling change is in a region of gp120 distal from the cleavage site. Antigenic characterization of the vari able-loop-deleted SOS gp140 proteins revealed that deletion of the variable loops uncovers cryptic, conserved neutralization epitopes near the corecep tor-binding site on gp120. These modified, disulfide-stabilized glycoprotei ns might be useful as immunogens.