Skip to content

Research at St Andrews

RNA virus attenuation by codon pair deoptimisation is an artefact of increases in CpG/UpA dinucleotide frequencies

Research output: Contribution to journalArticle

DOI

Open Access permissions

Open

Author(s)

F. Tulloch, N. J. Atkinson, David John Evans, M. D. Ryan, P. Simmonds

School/Research organisations

Abstract

Mutating RNA virus genomes to alter codon pair (CP) frequencies and reduce translation efficiency has been advocated as a method to generate safe, attenuated virus vaccines. However, selection for disfavoured CPs leads to unintended increases in CpG and UpA dinucleotide frequencies that also attenuate replication. We designed and phenotypically characterised mutants of the picornavirus, echovirus 7, in which these parameters were independently varied to determine which most influenced virus replication. CpG and UpA dinucleotide frequencies primarily influenced virus replication ability while no fitness differences were observed between mutants with different CP usage where dinucleotide frequencies were kept constant. Contrastingly, translation efficiency was unaffected by either CP usage or dinucleotide frequencies. This mechanistic insight is critical for future rational design of live virus vaccines and their safety evaluation; attenuation is mediated through enhanced innate immune responses to viruses with elevated CpG/UpA dinucleotide frequencies rather the viruses themselves being intrinsically defective.

Close

Details

Original languageEnglish
Article numbere04531
Number of pages15
JournaleLife
Volume3
Early online date9 Dec 2014
DOIs
Publication statusPublished - 9 Jan 2015

    Research areas

  • Escherichia-coli, Context analysis, Genome, Scale, CPG, Influenza, Selection, Bias, UPA, Replication

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Occurrence, prevalence and viral load of deformed wing virus variants in Apis mellifera colonies in Chile

    Riveros, G., Arismendi, N., Zapata, N., Evans, D., Pérez, I., Aldea, P. & Vargas, M., 9 Oct 2019, In : Journal of Apicultural Research. 59, 1, p. 63-68 6 p.

    Research output: Contribution to journalArticle

  2. Therapeutic applications of the 'NPGP' family of viral 2As

    Luke, G. A. & Ryan, M. D., Nov 2018, In : Reviews in Medical Virology. 28, 6, 12 p., e2001.

    Research output: Contribution to journalReview article

  3. Mechanisms and consequences of positive-strand RNA virus recombination

    Bentley, K. & Evans, D. J., 1 Oct 2018, In : Journal of General Virology. 99, 10, p. 1345-1356

    Research output: Contribution to journalReview article

Related by journal

  1. eLife (Journal)

    Will Cresswell (Reviewer)
    11 Apr 2018

    Activity: Publication peer-review and editorial work typesPeer review of manuscripts

  2. eLife (Journal)

    Christian Rutz (Member of editorial board)
    27 Jul 2016 → …

    Activity: Publication peer-review and editorial work typesEditor of research journal

Related by journal

  1. ATP-induced asymmetric pre-protein folding as a driver of protein translocation through the Sec machinery

    Corey, R., Ahdash, Z., Shah, A., Pyle, E., Allen, W., Fessl, T., Lovett, J. E., Politis, A. & Collinson, I., 2 Jan 2019, In : eLife. 8, 25 p., e41803.

    Research output: Contribution to journalArticle

  2. Improved characterisation of MRSA transmission using within-host bacterial sequence diversity

    Hall, M. D., Holden, M. TG., Srisomang, P., Mahavanakul, W., Wuthiekanun, V., Limmathurotsakul, D., Fountain, K., Parkhill, J., Nickerson, E. K., Peacock, S. J. & Fraser, C., 8 Oct 2019, In : eLife. 8

    Research output: Contribution to journalArticle

  3. Control of cyclic oligoadenylate synthesis in a type III CRISPR system

    Rouillon, C., Athukoralage, J. S., Graham, S., Grüschow, S. & White, M. F., 19 Jul 2018, In : eLife. 7, 22 p., e36734.

    Research output: Contribution to journalArticle

  4. Large-scale replication study reveals a limit on probabilistic prediction in language comprehension

    Nieuwland, M. S., Politzer-Ahles, S., Heyselaar, E., Segaert, K., Darley, E., Kazanina, N., Von Grebmer Zu Wolfsthurn, S., Bartolozzi, F., Kogan, V., Ito, A., Mézière, D., Barr, D. J., Rousselet, G. A., Ferguson, H. J., Busch-Moreno, S., Fu, X., Tuomainen, J., Kulakova, E., Husband, E. M., Donaldson, D. I. & 4 others, Kohút, Z., Rueschemeyer, S-A., Huettig, F. & Shinn-Cunningham, B. G. (ed.), 3 Apr 2018, In : eLife. 7, 24 p., e33468.

    Research output: Contribution to journalArticle

  5. Reactive oxygen species regulate activity-dependent neuronal plasticity in Drosophila

    Oswald, M. C., Brooks, P. S., Zwart, M. F., Mukherjee, A., West, R. J., Giachello, C. N., Morarach, K., Baines, R. A., Sweeney, S. T. & Landgraf, M., 17 Dec 2018, In : eLife. 7, 27 p., e39393.

    Research output: Contribution to journalArticle

ID: 161871167

Top