Inhibition of gp160 and CD4 maturation in U937 cells after both defective and productive infections by human immunodeficiency virus type 1.
Our results demonstrate that the formation of intracellular complexes between the envelope glycoprotein precursor gp160 of human immunodeficiency virus type 1 and CD4 is a major event, leading to the disappearance of CD4 at the cell surface of infected U937 cells. Using both productively and defectively infected clones of U937 cells, we assessed the effect of CD4-gp160 intracellular association on the maturation of both proteins. Pulse-chase labeling followed by sequential immunoprecipitation was used to analyze the processing of both free and associated CD4 and gp160, and the results showed that the trimming, proteolytic cleavage, and degradation of gp160 were completely abrogated after intracellular binding to CD4. Similarly, the maturation process which normally transforms 80% of CD4 to a partially endoglycosidase H-resistant species was also impaired subsequent to the formation of these complexes. A comparison of gp160 maturation either in free form or as a CD4 complex revealed that neither inefficient transport nor degradation of gp160 can account for the observed blockage of CD4 maturation. Moreover, this impairment was independent of gp120 and gp41, since a defective clone of human immunodeficiency virus type 1-infected cells, unable to cleave gp160, showed binding of CD4 and inhibition of CD4 transport and maturation with the same efficiency as occurred in productively infected cells. Expression of gp160 is thus necessary and sufficient to cause CD4 receptor down-modulation for both productively and defectively infected cells.
Lady Davis Institute-Jewish General Hospital, Montreal, Quebec, Canada.
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Wainberg
D015704:CD4 Antigens / Q000096:biosynthesis / Q000378:metabolism*; D002460:Cell Line; D002999:Clone Cells; D003673:Defective Viruses / Q000502:physiology*; D005434:Flow Cytometry; D015686:Gene Products, env / Q000096:biosynthesis / Q000378:metabolism*; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D011485:Protein Binding; D011498:Protein Precursors / Q000096:biosynthesis / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D014771:Virion / Q000502:physiology
D015704:CD4 Antigens; D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D014759:Viral Envelope Proteins