SMALL AMINO-ACID-SEQUENCE CHANGES WITHIN THE V2 DOMAIN CAN AFFECT THEFUNCTION OF A T-CELL LINE-TROPIC HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GP120

Prior studies with recombinant viruses constructed in vitro showed tha t the V2 domain of envelope gp120, in addition to the required V3 doma in, enhances the efficiency of infection of primary macrophages by HIV -1. Present structural studies on the gp120s of these recombinant Viru ses using three human monoclonal antibodies directed to the vs loop in dicate that the V2 domain affects cell tropism by modulating the confo rmation of the V3 loop. Additional mutational analyses of the V2 domai n of the T-cell line-tropic virus HIV-1(SF2) reveal that single amino acid sequence changes, mainly those affecting the location of potentia l N-linked glycosylation sites and the positive charge of this region, can also alter tropism. These amino acid substitutions in the V2 doma in, however, do not appear to alter the conformation of the V3 loop. T hus, the V2 domain of gp120 can influence cell tropism through both an effect on V3 as well as via a V3-independent mechanism. (C) 1995 Acad emic Press, Inc.