Protease activation during HIV infection in a CD4-positive cell line.
The mechanism of cytopathic effects associated with HIV infection in a continuous line of CD4-positive lymphocytes (CEM cells, clone 13) has been studied. Here we report the following observations: (1) HIV infection killed a variable but always significant number of cells without a strict relationship with the syncytia formation; (2) an important decrease in the proliferation rate occurred soon after infection; (3) a marked inhibition of protein synthesis took place within the first few hours of infection and clearly before the beginning of viral protein expression. In addition, when three-day-old cultures were incubated in serum-free medium, a larger degradation of proteins was observed in infected cells in comparison to controls. An increase in protein degradation activity was observed also in vitro with extracts obtained from HIV-infected cells and incubated in the presence of endogenous- or exogenous-labeled substrates. Extracts from cells infected with heat-inactivated HIV did not show a similar degradative activity. The possible induction or activation of latent proteases during the development of the HIV infection is discussed.
Piedimonte
G
G
Istituto di Patologia Generale, University of Parma, Italy.
Petronini
P G
PG
Guetard
D
D
Favier
V
V
Borghetti
A F
AF
Montagnier
L
L
D015704:CD4 Antigens / Q000276:immunology; D002470:Cell Survival; D002675:Child, Preschool; D003588:Cytopathogenic Effect, Viral; D010450:Endopeptidases / Q000096:biosynthesis*; D004789:Enzyme Activation / Q000187:drug effects; D015684:Gene Products, pol / Q000096:biosynthesis*; D015658:HIV Infections / Q000201:enzymology*; D016333:HIV Protease; D015497:HIV-1 / Q000201:enzymology* / Q000276:immunology / Q000502:physiology; D006801:Humans; D007700:Kinetics; D007958:Leukocyte Count; D011480:Protease Inhibitors / Q000494:pharmacology; D011489:Protein Denaturation; D014407:Tumor Cells, Cultured
D015704:CD4 Antigens; D015684:Gene Products, pol; D011480:Protease Inhibitors; D010450:Endopeptidases; D016333:HIV Protease