GENERATION OF LYMPHOCYTE CELL-LINES COEXPRESSING CD4 AND WILD-TYPE ORMUTANT HIV TYPE-1 GLYCOPROTEINS - IMPLICATIONS FOR HIV TYPE-1 ENV-INDUCED CELL-LYSIS

To gain more insight into the processes leading to HIV-1 Env-induced c ell death, we aim to coexpress stably wild-type and relevant mutant va riants of both HIV-1 Env and human CD4 in lymphocyte cell lines. Here we report on the generation and characterization of several cell lines inducibly or constitutively expressing wildtype or cleavage-defective HIV-1 glycoproteins and human CD4 either singly or in combination, Co expression of CD4 and wild-type Env led to the formation of multinucle ated syncytia, to growth arrest and cell death, effects that all could be prevented by cultivation in the presence of monoclonal antibodies that inhibit cell surface membrane fusion. Cell lines coexpressing CD4 and mutated, noncleavable Env, detectable at the cell surface and sti ll retaining CD4-binding capacity, were not retarded in their growth a nd cytolysis did not occur. These results indicate that cell lysis req uires cell surface interaction of CD4 and gp120/41 and cleavage of gp1 60 to gp120 and gp41.