DUTPASE-MINUS CAPRINE ARTHRITIS-ENCEPHALITIS VIRUS IS ATTENUATED FOR PATHOGENESIS AND ACCUMULATES G-TO-A SUBSTITUTIONS

The importance of the virally encoded dUTPase for CAEV replication, in vasiveness, pathogenesis, and genetic stability was investigated in go ats infected by viruses with single point (DU-G) and deletion (DU-1) m utations of the dUTPase gene (DU gene). The DU gene was found to be di spensable for CAEV replication in vivo as judged by times taken to ser oconvert, frequencies of viral isolation, and tissue distribution of v iral RNAs. DU- reversion at week 34 in one of three goats infected wit h the single point mutant DU-G, however, suggested that the viral dUTP ase confers some advantages for replication in vivo. Moreover, we show that dUTPase is necessary for the timely development of bilateral art hritic lesions of the carpus. Finally, dUTPase was shown to efficientl y prevent accumulation of G-to-A transitions in the viral genome.