CLEAVAGE OF NASCENT REOVIRUS MESSENGER-RNA BY LOCALIZED ACTIVATION OF THE 2'-5'-OLIGOADENYLATE-DEPENDENT ENDORIBONUCLEASE

Addition of cell extracts prepared from untreated or interferon-treated mouse L cells reduced the yield of reovirus RNA synthesized in transcription reactions with purified virions. The reduction observed with the extract of interferon-treated cells was greater than that observed with the extract of untreated cells. The yield of reovirus RNA could be restored to the level obtained without addition of cell extracts by carrying out transcription either in the presence of an inhibitor of 2''-5''-oligoadenylate (2-5A) synthesis, 2''-dATP or in the presence of the 3''-methyl analog of 5''-monophosphate 2-5A, which inhibits the 2-5A-dependent endoRNase. This enzyme was activated in a localized way since neither mRNA added to transcription reactions containing the extract of interferon-treated cells nor rRNA was appreciably degraded; accumulation of reovirus mRNA was drastically inhibited. These findings provide evidence for an antiviral role of the 2-5A synthetase/endoRNase system, which preferentially cleaves nascent viral RNA.