Publication Database

Mechanism of virus attenuation by codon pair deoptimization (2020)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Groenke, Nicole (WE 5)

Trimpert, Jakob (WE 5)

Merz, Sophie (WE 12)

Conradie, Andelé M. (WE 5)

Wyler, Emanuel

Zhang, Hongwei (WE 6)

Hazapis, Orsalia-Georgia

Rausch, Sebastian (WE 6)

Landthaler, Markus

Osterrieder, Nikolaus (WE 5)

Kunec, Dusan (WE 5)

Quelle

Cell reports

Bandzählung: 31

Heftzählung: 4

Seiten: 107586

ISSN: 2211-1247

Sprache

Englisch

Verweise

URL (Volltext): https://www.sciencedirect.com/science/article/pii/S2211124720305350

DOI: 10.1016/j.celrep.2020.107586

Pubmed: 32348767

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.