COUPLING BETWEEN GENOME TRANSLATION AND REPLICATION IN AN RNA VIRUS

The replication of poliovirus RNA genomes containing amber mutations w as studied to test whether viral proteins provided in trans could resc ue the replication of an RNA genome that could not be completely trans lated itself. Mutants containing amber codons at different positions i n the genome displayed vastly different abilities to be rescued by wil d-type proteins provided by a helper genome. Amber-suppressing cell li nes were used to ensure that the defects in the amber mutants arose fr om 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 regio n was shown to inhibit RNA replication. This coupling between translat ion and RNA replication could provide a late proofreading mechanism th at enables poliovirus, and possibly many other RNA viruses, to prevent the replication of defective genomes.