Synonymous Virus Genome Recoding as a Tool to Impact Viral Fitness

Synthetic genome recoding is a novel method of generating viruses with altered phenotypes, whereby many synonymous mutations are introduced into the protein coding region of the virus genome without altering the encoded proteins. Virus genome recoding with large numbers of slightly deleterious mutations has produced attenuated forms of several RNA viruses. Virus genome recoding can also aid in investigating virus interactions with innate immune responses, identifying functional virus genome structures, strategically ameliorating cis-inhibitory signaling sequences related to complex viral functions, to unravel the relevance of codon usage for the temporal regulation of viral gene expression and improving our knowledge of virus mutational robustness and adaptability. The present review discusses the impacts of synonymous genome recoding with regard to expanding our comprehension of virus biology, and the development of new and better therapeutic strategies.

TrendsChemical synthesis of viral genomes without a natural template is a useful tool for genetic modification on a large scale.Attenuated viruses can be obtained by synonymously redesigning virus genomes based on changes in codon usage, codon pair usage, and/or dinucleotide content.Synonymously recoding of viruses may lead to the generation of new classes of live attenuated vaccines.In vaccines generated by synonymous recoding, all viral proteins are encoded with wild-type amino acid sequences that are exactly the same.Synonymous virus genome recoding involves hundreds or thousands of nucleotide substitutions, possibly reducing the risk of virus phenotypic reversion via point mutations.Large-scale synonymous recoding of virus genomes is a new tool that can assist in exploring different aspects of virus biology.