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 and steady-state levels of both CD4 protein and mRNA in a variety of clonal derivatives of U-937 cells, chronically infected with human immunodeficiency virus type 1 IIIB (HIV-1), that express various cellular and viral phenotypes. These phenotypes included defective processing of either gp160 or Gag-Pol, viruses with severely limited host-range, and inability to generate viral products. All clones, with the exception of the one that failed to generate viral mRNA and proteins, did not express cell surface CD4. Furthermore, each of these clones had steady-state levels of CD4 mRNA which were either equivalent to or higher than those of the parental U-937 cell line. Patterns of cytoplasmic CD4 mRNA levels resembled those of total RNA, suggesting that CD4 mRNA transport from the nucleus to the cytoplasm was unaffected by HIV-1 infection. Profiles of steady-state levels of the CD4 protein resembled those of CD4 mRNA in the UHC clones, but CD4 biosynthesis was reduced in all clones with the exception of that which failed to express viral products. This report is the first demonstration that steady-state CD4 biosynthesis is reduced in HIV-1-infected cells. In general, there was a good correlation between high levels of expression of gp160 and reduced CD4 biosynthesis. These results suggest that HIV-1 env gene products may contribute to the observed reduction in levels of CD4 biosynthesis.
Geleziunas
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R
McGill AIDS Centre, Lady Davis Institute-Jewish General Hospital, Montreal, Canada.
Bour
S
S
Wainberg
M A
MA
D015152:Blotting, Northern; D015704:CD4 Antigens / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D015686:Gene Products, env / Q000032:analysis / Q000378:metabolism*; D015693:Gene Products, nef / Q000032:analysis; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000378:metabolism*; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D009000:Monocytes / Q000276:immunology / Q000382:microbiology*; D011498:Protein Precursors / Q000032:analysis / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011863:Radioimmunoassay; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D054334:Viral Regulatory and Accessory Proteins / Q000032:analysis; D054311:nef Gene Products, Human Immunodeficiency Virus; D000086082:Viroporin Proteins
D015704:CD4 Antigens; D015686:Gene Products, env; D015693:Gene Products, nef; D019302:HIV Envelope Protein gp160; D054298:Human Immunodeficiency Virus Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D054334:Viral Regulatory and Accessory Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins