Interactions between retroviruses associated with acquired immunodeficiency syndrome and their receptors on lymphocytes represent the initial steps in the process of infection and are also involved in multinucleated giant cell formation, which is one form of virus-mediated cytopathology. The exterior envelope glycoprotein of the retrovirus has been identified as gpl20, and we demonstrate here that purified gpl20 binds directly to cells expressing the CD4 (T4) surface antigen at a site spatially related to that recognized by the OKT4A monoclonal antibody. The gpl20 Was also able to temporarily interfere with viral infection and to block the process of multinucleated giant cell formation. However, if the carbohydrate chains were removed from gpl20 by enzymatic treatment, CD4 binding and blockade of cell fusion was reduced by about a factor of 50. The significance of these results in relation to preventive and interventive approaches for acquired immunodeficiency syndrome is discussed.Human immunodeficiency virus is the generic name for a family of lymphotropic retroviruses (1) whose primary target is the helper/inducer subset of T-lymphocytes bearing the CD4 cell surface marker (2-6). The actual mechanism by which the virus infects susceptible target cells is beginning to be understood. Quite remarkably, monoclonal antibodies to certain epitopes of CD4 can block infection (7-9) and can immunoprecipitate complexes of CD4 and gp120, the major envelope glycoprotein of the infecting virus (10). These results suggest that a key interaction between gpl20 and CD4 initiates the infectious process.

The lymphocyte differentiation antigen CD4 serves as a receptor for human retroviruses associated with acquired immunodeficiency syndrome (AIDS) through its interaction with the major envelope virion glycoprotein, gpl20, which is also expressed on the surface of infected cells. In these experiments, purified gpl20 was shown to bind to normal human T-lymphocyte populations. The gpl2O-CD4 complex served as a target antigen for antibody-dependent complementmediated cytolysis by a goat serum raised against native gpl20. However, patient sera that bound to gpl20-adsorbed cells failed to direct their destruction in the presence of complement. In contrast, these sera were potent mediators of antibodydependent cellular cytotoxicity. These studies demonstrate that gpl20 situated on the cell surface can serve as an effective target for immune destruction by patient antibodies and effector lymphocytes. The possible contribution of this type of immunity to control of disease progression, on the one hand, and to lymphocyte destruction and immunopathology observed in AIDS, on the other, is discussed.The most profound hematologic feature associated with acquired immunodeficiency syndrome (AIDS) is the functional impairment and quantitative depletion of the subset of lymphocytes that express the CD4 surface antigen (1-6). Infection of CD4 cells in vitro results in the rapid spread of virus throughout the culture and subsequent cell death due to the as yet undefined process of virus-induced cytopathology (7)(8)(9)(10)(11)(12) The current body of evidence suggests that the T-cell lymphotropic properties of the causative agent virus are due, in large part, to the interaction between the major virion envelope glycoprotein (gp120) and specific epitopes of the CD4 antigen complex. Monoclonal antibodies directed against particular determinants of CD4 have been shown to block both infection (14, 15) and multinucleated giant cell formation (16), in addition to precipitating gpl2O-CD4 complexes from infected cells (17). Recent studies revealed that purified gpl20 can effectively block cell fusion, most likely by competing for available CD4 sites on noninfected cells (18). In addition, purified gpl20 readily associates with the CD4 molecules and forms a stable complex on the cell surface (19). This latter finding suggested the possibility that free gpl20 bound to noninfected CD4-expressing lymphocytes could serve as a potential target for immune attack resulting in subsequent lympholysis. MATERIALS AND METHODSCells. Normal CD4-positive lymphocyte populations (CD4 cells) were obtained by stimulating normal donor peripheral blood mononuclear cells with tetanus toxoid for 5 days, sorting for CD4 expression, and expanding in the presence of recombinant interleukin 2. CEM cell lines (CEM) or human T-cell lymphotropic virus IIIB (HTLV-IIIB)t chronically infected CEM (CEM/IIIB) have been described (19). gpl20 and Goat gpl2O Antisera. The gp120 was isolated from HTLV-IIIn-infected H9 cells as described (18). Briefly, cells were lysed with...

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