ANALYSIS OF THE INTERACTION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP120 ENVELOPE GLYCOPROTEIN WITH THE GP41 TRANSMEMBRANE GLYCOPROTEIN

The human immunodeficiency virus type 1 (HIV-1) gp120 exterior envelop e glycoprotein interacts with the viral receptor (CD4) and with the gp 41 transmembrane envelope glycoprotein. To study the interaction of th e gp120 and gp41 envelope glycoproteins, we compared the abilities of anti-gp120 monoclonal antibodies to bind soluble gp120 and a soluble g lycoprotein, sgp140, that contains gp120 and gp41 exterior domains. Th e occlusion or alteration of a subset of gp120 epitopes on the latter molecule allowed the definition of a gp41 ''footprint'' on the gp120 a ntibody competition map. The occlusion of these epitopes on the sgp140 glycoprotein was decreased by the binding of soluble CD4. The gp120 e pitopes implicated in the interaction with the gp41 ectodomain were di srupted by deletions of the first (C1) and fifth (C5) conserved gp120 regions. These deletions did not affect the integrity of the discontin uous binding sites for CD4 and neutralizing monoclonal antibodies. Thu s, the gp41 interface on the HIV-1 gp120 glycoprotein, which elicits n onneutralizing antibodies, can be removed while retaining immunologica lly desirable gp120 structures.