Mechanism of Virus Attenuation by Codon Pair Deoptimization

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

5 Scopus Citations
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Author(s)

  • Nicole Groenke
  • Jakob Trimpert
  • Sophie Merz
  • Andelé M. Conradie
  • Emanuel Wyler
  • Hongwei Zhang
  • Orsalia-Georgia Hazapis
  • Sebastian Rausch
  • Markus Landthaler
  • Dusan Kunec

Detail(s)

Original languageEnglish
Article number107586
Journal / PublicationCell Reports
Volume31
Issue number4
Online published28 Apr 2020
Publication statusPublished - 28 Apr 2020
Externally publishedYes

Abstract

Codon pair deoptimization is an efficient virus attenuation strategy, but the mechanism that leads to attenuation is unknown. The strategy involves synthetic recoding of viral genomes that alters the positions of synonymous codons, thereby increasing the number of suboptimal codon pairs and CpG dinucleotides in recoded genomes. Here we identify the molecular mechanism of codon pair deoptimization-based attenuation by studying recoded influenza A viruses. We show that suboptimal codon pairs cause attenuation, whereas the increase of CpG dinucleotides has no effect. Furthermore, we show that suboptimal codon pairs reduce both mRNA stability and translation efficiency of codon pair-deoptimized genes. Consequently, reduced protein production directly causes virus attenuation. Our study provides evidence that suboptimal codon pairs are major determinants of mRNA stability. Additionally, it demonstrates that codon pair bias can be used to increase mRNA stability and protein production of synthetic genes in many areas of biotechnology.

Research Area(s)

  • attenuation, codon bias, codon pair bias, codon pair deoptimization, dinucleotide frequencies, influenza A virus, mRNA stability, recoding, synthetic attenuated virus engineering

Citation Format(s)

Mechanism of Virus Attenuation by Codon Pair Deoptimization. / Groenke, Nicole; Trimpert, Jakob; Merz, Sophie; Conradie, Andelé M.; Wyler, Emanuel; Zhang, Hongwei; Hazapis, Orsalia-Georgia; Rausch, Sebastian; Landthaler, Markus; Osterrieder, Nikolaus; Kunec, Dusan.

In: Cell Reports, Vol. 31, No. 4, 107586, 28.04.2020.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review