SERA FROM HIV-1-INFECTED INDIVIDUALS IN ALL STAGES OF DISEASE PREFERENTIALLY RECOGNIZE THE V3 LOOP OF THE PROTOTYPIC MACROPHAGE-TROPIC GLYCOPROTEIN GP120 ADA

The outer membrane glycoprotein gp120 and the transmembrane glycoprote in gp41 are predominant targets of the humoral immune response to infe ction by human immunodeficiency virus type 1. The third hypervariable region (V3 loop) is the principal neutralizing domain and is the prima ry target of neutralizing antibodies directed against the envelope pro teins of HIV-1. The V3 loop is also the major determinant for HIV-1 ce ll-specific tropism. To further characterize the humoral immune respon se directed against the gp120 envelope proteins, we expressed two prot otypic gp120 envelope proteins (LAI/HXB2 and ADA) and chimeric gp 120 envelope proteins in stable transfected Drosophila melanogaster Schnei der 2 cells. Sera from four infected adults over the course of infecti on [McNearney et al. (1992) Proc, natn. Acad. Sci. U.S.A. 89, p. 10,24 2] were assayed for reactivity with the respective envelope proteins. Sera obtained at early stages preferentially recognized the gp120 enve lope protein ADA, whereas in later stages of infection the sera showed diminished reactivity with both gp120 LAI/HXB2 and gp120 ADA. Chimeri c envelope proteins revealed that the humoral response was directed pr imarily against the V3 loop of gp120 ADA. Furthermore, 22 sera from HI V-1 infected individuals in different stages of the disease were teste d. Reactivity of sera with the gp120 envelope protein ADA was seven-fo ld higher than with the gp120 envelope protein LAI/HXB2. Our results s uggest that the humoral immune response is preferentially elicited aga inst the V3 loop of the prototypic macrophage-tropic gp 120 envelope p rotein ADA.