Coding changes in the poliovirus protease 2A compensate for 5 ' NCR domainV disruptions in a cell-specific manner

Polioviruses are single-stranded RNA viruses with an unusually long noncodi ng region (NCR) at the 5' end predicted to have an elaborate secondary stru cture made up of six domains. Mutations In domain V of the poliovirus 5'NCR that disrupt secondary structure are responsible for attenuation of the vi rus and a temperature-sensitive (ts) phenotype in vitro. In addition to dir ect back mutation or compensatory second site mutation In the 5'NCR as prev iously documented, the ts phenotype was found to he compensated for in monk ey kidney cells in vitro by a coding change In the protease 2A. These codin g changes were found throughout the protease with no obvious pattern or tre nd. They were not all found to be equivalent and limited in ability to comp ensate for the severest domain V disruption. The compensatory effect of the 2A changes was found to be cell specific, having no effect on monkey neuro virulence and in a mouse cell line but a significant effect in two monkey c ell lines and a human epithelial line, (C) 2000 Academic Press.