Coupling between genome translation and replication in an RNA virus.

The replication of poliovirus RNA genomes containing amber mutations was studied to test whether viral proteins provided in trans could rescue the replication of an RNA genome that could not be completely translated itself. Mutants containing amber codons at different positions in the genome displayed vastly different abilities to be rescued by wild-type proteins provided by a helper genome. Amber-suppressing cell lines were used to ensure that the defects in the amber mutants arose from their failure to be translated, not from defects in RNA sequence or structure. An internal region of the poliovirus genome was identified whose translation is required in cis; failure to translate this region was shown to inhibit RNA replication. This coupling between translation and RNA replication could provide a late proofreading mechanism that enables poliovirus, and possibly many other RNA viruses, to prevent the replication of defective genomes.