Hypermutation of the phosphoprotein and altered mRNA editing in the hamster neurotropic strain of measles virus.

Sequence analysis of the nucleoprotein and phosphoprotein (P) genes of viruses in the hamster neurotropic lineage of measles virus revealed that the neurotropic variants are quite different from the Philadelphia 26 progenitor strain. In Vero cells persistently infected with the hamster neurotropic strain, predicted changes occur in 5.0% of the nucleoprotein and 8.1% of the P amino acids and some of these changes appear to affect the relative electrophoretic mobility of each protein. To evaluate one aspect of the viral polymerase complex containing these mutations, the distribution of P mRNA editing in each of the three strains was determined by both cloning and sequencing of polymerase chain reaction-amplified DNA fragments which included the editing site and by primer extension analysis of viral mRNA. Editing of P mRNA in the neurotropic strains shows a shift away from the single G insertion product to those with greater than 2 Gs inserted. The altered editing distribution has implications for the role of transcriptional regulation in measles virus persistence.