PROCESSING OF THE ENVELOPE GLYCOPROTEIN GP160 IN IMMUNOTOXIN-RESISTANT CELL-LINES CHRONICALLY INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

We describe the isolation and characterization of variant cell lines w hich are chronically infected with the human immunodeficiency virus (H IV) and resistant to the action of immunotoxins directed against the H IV envelope protein, These variants all produce normal levels of HN pr oteins, budding virions, and the envelope protein precursor gp160. Two of the variants, 10E and 11E, contain a mutation within the env gene which results in the production of a truncated precursor and altered p rocessing and transport of the protein to the fell surface, Variants B 9 and G4 are defective in gp160 cleavage and do not efficiently transp ort the envelope protein to the cell surface, There are no mutations i n the expressed viruses of B9 and G4, These cell lines express higher levels of CD4 protein and mRNA than H9/NL4-3. Thus 10E, 11E, B9, and G 4 have escaped immunotoxin action by downmodulating the envelope prote in from their cell surfaces, None of these variants produce infectious HIV. Two other immunotoxin-resistant variants, E9-3 and 41-17, produc e normal levels of gp160, efficiently transport the cleaved and proces sed subunits to the cell surface, and secrete infectious HIV. These st udies identify alterations in gp160 processing that underscore the imp ortance of the relationship between HIV and the cell that it infects.