CORRELATION BETWEEN HIGH-LEVEL GP160 EXPRESSION AND REDUCED CD4 BIOSYNTHESIS IN CLONAL DERIVATIVES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-INFECTED U-937 CELLS

We have compared cytoplasmic CD4 mRNA accumulation, CD4 biosynthesis a nd steady-state levels of both CD4 protein and mRNA in a variety of cl onal derivatives of U-937 cells, chronically infected with human immun odeficiency virus type 1 IIIB (HIV-I), that express various cellular a nd viral phenotypes. These phenotypes included defective processing of either gp160 or Gag-Pol, viruses with severely limited host-range, an d inability to generate viral products. Ah clones, with the exception of the one that failed to generate viral mRNA and proteins, did not ex press cell surface CD4. Furthermore, each of these clones had steady-s tate levels of CD4 mRNA which were either equivalent to or higher than those of the parental U-937 cell line. Patterns of cytoplasmic CD4 mR NA levels resembled those of total RNA, suggesting that CD4 mRNA trans port from the nucleus to the cytoplasm was unaffected by HIV-1 infecti on. Profiles of steady-state levels of the CD4 protein resembled those of CD4 mRNA in the UHC clones, but CD4 biosynthesis was reduced in al l clones with the exception of that which failed to express viral prod ucts. This report is the first demonstration that steady-state CD4 bio synthesis is reduced in HIV-1-infected cells. In general, there was a good correlation between high levels of expression of gp160 and reduce d CD4 biosynthesis. These results suggest that HIV-1 env gene products may contribute to the observed reduction in levels of CD4 biosynthesi s.