Abstract
ABSTRACTThe development of safe and effective vaccines against viruses is central to disease control. With advancements in DNA synthesis technology, the production of synthetic viral genomes has fueled many research efforts that aim to generate attenuated viruses by introducing synonymous mutations. Elucidation of the mechanisms underlying virus attenuation through synonymous mutagenesis is revealing interesting new biology that can be exploited for vaccine development. Here, we review recent advancements in this field of synthetic virology and focus on the molecular mechanisms of attenuation by genetic recoding of viruses. We highlight the action of the zinc finger antiviral protein (ZAP) and RNase L, two proteins involved in the inhibition of viruses enriched for CpG and UpA dinucleotides, that are often the products of virus recoding algorithms. Additionally, we discuss current challenges in the field as well as studies that may illuminate how other host functions, such as translation, are potentially involved in the attenuation of recoded viruses.
Highlights
The development of safe and effective vaccines against viruses is central to disease control
Further investigation is required to tease apart the effects of codon and codon pair deoptimization and increases of CpG/UpA dinucleotides on viral replication
Modifications involving CpG and UpA dinucleotide enrichment led to the discovery of important antiviral mechanisms, such as zinc finger antiviral protein (ZAP)-mediated and RNase L-mediated viral RNA degradation, which appear to be central mechanisms for the attenuation of recoded viruses
Summary
The development of safe and effective vaccines against viruses is central to disease control. Increased levels of CpG/UpA dinucleotides have been found to be deleterious for virus replication in both coding and noncoding regions of RNA molecules [36, 42, 43]. Further investigation is required to tease apart the effects of codon and codon pair deoptimization and increases of CpG/UpA dinucleotides on viral replication.
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