Inactivation of Genes by Frameshift Mutations Provides Rapid Adaptation of an Attenuated Vaccinia Virus.

ABSTRACT: Unlike RNA viruses, most DNA viruses replicate their genomes with high-fidelity polymerases that rarely make base substitution errors. Nevertheless, experimental evolution studies have revealed rapid acquisition of adaptive mutations during serial passage of attenuated vaccinia virus (VACV). One way in which adaptation can occur is by an accordion mechanism in which the gene copy number increases followed by base substitutions and, finally, contraction of the gene copy number. Here, we show rapid acquisition of multiple adaptive mutations mediated by a gene-inactivating frameshift mechanism during passage of an attenuated VACV. Attenuation had been achieved by exchanging the VACV A8R intermediate transcription factor gene with the myxoma virus ortholog. A total of seven mutations in six di

SUBMITTER: Senkevich TG 

PROVIDER: S-EPMC7459559 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature