PEPTIDYL-TRANSFERASE INHIBITORS HAVE ANTIVIRAL PROPERTIES BY ALTERINGPROGRAMMED -1-RIBOSOMAL FRAMESHIFTING EFFICIENCIES - DEVELOPMENT OF MODEL SYSTEMS

The effects of two peptidyl-transferase inhibitors, anisomycin and spa rsomycin, on ribosomal frameshifting efficiencies and the propagation of yeast double-stranded RNA viruses were examined. At sublethal doses in yeast cells these drugs specifically alter the efficiency of -1, b ut not of +1, ribosomal frameshifting. These compounds promote loss of the yeast L-A double-stranded RNA virus, which uses a programmed -1 r ibosomal frameshift to produce its Gag-Pol fusion protein, Both of the se drugs also change the efficiency of -1 ribosomal frameshifting in y east and mammalian in vitro translation systems, suggesting that they may have applications to control the propagation of viruses of higher eukaryotes, which also use this translational regulatory mechanism, Ou r results offer a nem set of antiviral agents that may potentially hav e a broad range of applications in the clinical, veterinary, and agric ultural fields.