Comparison of the Antiviral Efficacy of Ribozymes and Antisense RNA Directed Against Bovine Leukemia Virusrex/tax

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Abstract
Despite the theoretical attraction of ribozymes, which cleave their target RNA, as compared with antisense RNA, which only blocks translation, few studies have assessed the relative efficacy of ribozymes and antisense RNA directed against the identical target sequence. Previously, we described the efficacy of a hammerhead ribozyme targeted against rex/tax, a regulatory gene of bovine leukemia virus (BLV). In this study, we asked whether antisense RNA targeted against the same site would also be efficacious. BLV-infected bat lung cells were transfected with an antisense RNA-encoding plasmid under the control of the Rous sarcoma virus (RSV) promoter, and stable cell lines were selected. No inhibition of viral p24 expression was demonstrated in seven cell lines transfected with the antisense RNA targeted at the same site as the ribozyme or in three cell lines transfected with an antisense sequence targeted against the tax 5‵ initiation codon. Although in previous experiments antisense DNA oligonucleotides inhibited Tax expression in vitro, stably transfected plasmids encoding antisense RNA of the same sequence did not inhibit viral expression in BLV-infected cells in this study. These results suggest that in persistently infected cells producing high levels of BLV, the ribozyme is more effective than antisense RNA directed at rex/tax transcripts.