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Effects of protease inhibitors on chemical induction of type C virus
Abstract:
A role for proteolysis during chemical induction of endogenous xenotropic Type C virus from Kirsten sarcoma virus-transformed mouse cells was examined. Two distinct classes of protease inhibitors, the trypsin inhibitor, alpha-N-tosyl-L-lysine chloromethyl ketone, and two naturally occurring oligopeptide inhibitors, antipain and leupeptin, were found to inhibit induction of virus by cycloheximide and histidinol. Virus activation by 5-iododeoxyuridine was inhibited to a lesser degree. During the time cells were exposed to these compounds, there was little inhibition of [3H]uridine incorporation into total cellular RNA or polyadenylic acid cytoplasmic messenger RNA, suggesting that inhibition of proteolysis, and not RNA transcription, was responsible for blocking virus induction.
Insights
Protease inhibitors block the chemical induction of endogenous xenotropic Type C virus in transformed mouse cells. This suggests proteolysis, not RNA transcription, is key for virus activation.
Area of Science:
- Virology
- Molecular Biology
- Biochemistry
Background:
- Kirsten sarcoma virus transformation induces endogenous xenotropic Type C virus in mouse cells.
- Viral induction can be triggered by chemical agents like cycloheximide and histidinol.
- The precise molecular mechanisms underlying viral induction are not fully understood.
Purpose of the Study:
- To investigate the role of proteolysis in the chemical induction of endogenous xenotropic Type C virus.
- To determine if inhibiting proteolysis affects viral induction by specific chemical agents.
Main Methods:
- Utilized Kirsten sarcoma virus-transformed mouse cells.
- Administered chemical inducers: cycloheximide, histidinol, and 5-iododeoxyuridine.
- Applied protease inhibitors: alpha-N-tosyl-L-lysine chloromethyl ketone, antipain, and leupeptin.
- Measured [3H]uridine incorporation into cellular RNA to assess transcription inhibition.
Main Results:
- Protease inhibitors significantly inhibited virus induction by cycloheximide and histidinol.
- Viral activation by 5-iododeoxyuridine was less affected by protease inhibitors.
- Inhibitors showed minimal impact on [3H]uridine incorporation, indicating RNA transcription was not the primary target.
Conclusions:
- Proteolysis plays a critical role in the chemical induction of endogenous xenotropic Type C virus.
- Inhibition of proteolysis effectively blocks viral induction, suggesting it's a necessary step.
- The findings differentiate the mechanism of induction by different chemical agents.