Target cell-specific determinants of membrane fusion within the human immunodeficiency virus type 1 gpl20 third variable region and gp41 amino terminus

The entry of human immunodeficiency virus type 1 (HIV-1) into target cells involves binding to the viral receptor (CD4) and membrane fusion events, the latter influenced by target cell factors other than CD4. The third variable (V3) region of the HlV-1 gpl20 exterior envelope glycoprotein and the amino terminus of the HIV-1 gp4l transmembrane envelope glycoprotein have been shown to be important for the membrane fusion process. Here we demonstrate that some HIV-1 envelope glycoproteins containing an altered V3 region or gp4l amino terminus exhibit qualitatively different abilities to mediate syncytium formation and virus entry when different target cells are used. These results demonstrate that the structure of these HIV-1 envelope glycoprotein regions determines the efficiency of membrane fusion in a target cell-specific manner and support a model in which the gp4l amino terminus interacts directly or indirectly with the target cell during virus entry. Human immunodeficiency virus type 1 (HIV-1) is the etiologic agent of AIDS, which is characterized by a deple-tion of CD4-positive lymphocytes (2, 11, 13, 24, 35). HIV-1 exhibits a tropism for CD4-positive cells owing to a high-affinity interaction between the CD4 glycoprotein, which serves as the viral receptor, and the HIV-1 gpl20 exterio