A role for proteolysis during chemical induction of endogenous xenotropic Type C virus from Kirsten sarcoma virustransformed mouse cells was examined. Two distinct classes of protease inhibitors, the trypsin inhibitor, α-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.

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This work was supported by Contract N01-CO-75380 with the National Cancer Institute, NIH, Bethesda, Md. 20205.

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