Rescue of codon-pair deoptimized respiratory syncytial virus by the emergence of genomes with very large internal deletions that complemented replication.

ABSTRACT: Recoding viral genomes by introducing numerous synonymous but suboptimal codon pairs-called codon-pair deoptimization (CPD)-provides new types of live-attenuated vaccine candidates. The large number of nucleotide changes resulting from CPD should provide genetic stability to the attenuating phenotype, but this has not been rigorously tested. Human respiratory syncytial virus in which the G and F surface glycoprotein ORFs were CPD (called Min B) was temperature-sensitive and highly restricted in vitro. When subjected to selective pressure by serial passage at increasing temperatures, Min B substantially regained expression of F and replication fitness. Whole-genome deep sequencing showed many point mutations scattered across the genome, including one combination of six linked point mutation

SUBMITTER: Le Nouen C 

PROVIDER: S-EPMC8020775 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature