RAPID SELECTION FOR AN N-LINKED OLIGOSACCHARIDE BY MONOCLONAL-ANTIBODIES DIRECTED AGAINST THE V3 LOOP OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

The V3 loop of the human immunodeficiency virus (HIV) surface protein, gp120, constitutes a principal neutralizing determinant. HIV strains lacking a naturally conserved N-linked oligosaccharide (at position 30 6) within the V3 loop are highly sensitive to neutralization. We subje cted molecular clones of HIVLAI, lacking this N-306-glycan to in vitro immune selection with MAbs directed against the V3 loop. In all, ten clones were characterized, and all proved resistant to V3-directed neu tralization. Sequencing of the V3 loop revealed that six of the clones had become resistant at least partly by reacquisition of the N-306-gl ycan. Only two of the clones possessed mutations within the binding si te of the antibody itself, while the two remaining clones did not disp lay changes within the V3 loop itself. Thus, HIV strains lacking the N -306-glycan primarily develop resistance to V3-directed neutralization through acquisition of the specific oligosaccharide. This demonstrate s that protein glycosylation can be a primary modifier of virus antige nicity of possible importance for the interaction of HN with the host immune response.