Deep sequencing of foot-and-mouth disease virus reveals RNA sequences involved in genome packaging

Logan, G., Newman, J., Wright, C. F., Lasecka-Dykes, L., Haydon, D. T. , Cottam, E. M. and Tuthill, T. J. (2018) Deep sequencing of foot-and-mouth disease virus reveals RNA sequences involved in genome packaging. Journal of Virology, 92(1), e01159-17. (doi: 10.1128/JVI.01159-17) (PMID:29046452) (PMCID:PMC5730773)

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Abstract

Non-enveloped viruses protect their genomes by packaging them into an outer shell or capsid of virus-encoded proteins. Packaging and capsid assembly in RNA viruses can involve interactions between capsid proteins and secondary structures in the viral genome as exemplified by the RNA bacteriophage MS2 and as proposed for other RNA viruses of plants, animals and human. In the picornavirus family of non-enveloped RNA viruses, the requirements for genome packaging remain poorly understood. Here we show a novel and simple approach to identify predicted RNA secondary structures involved in genome packaging in the picornavirus foot-and-mouth disease virus (FMDV). By interrogating deep sequencing data generated from both packaged and unpackaged populations of RNA we have determined multiple regions of the genome with constrained variation in the packaged population. Predicted secondary structures of these regions revealed stem loops with conservation of structure and a common motif at the loop. Disruption of these features resulted in attenuation of virus growth in cell culture due to a reduction in assembly of mature virions. This study provides evidence for the involvement of predicted RNA structures in picornavirus packaging and offers a readily transferable methodology for identifying packaging requirements in many other viruses. Importance: In order to transmit their genetic material to a new host, non-enveloped viruses must protect their genomes by packaging them into an outer shell or capsid of virus-encoded proteins. For many non-enveloped RNA viruses the requirements for this critical part of the viral life cycle remain poorly understood. We have identified RNA sequences involved in genome packaging of the picornavirus foot-and-mouth disease virus. This virus causes an economically devastating disease of livestock affecting both the developed and developing world. The experimental methods developed to carry out this work are novel, simple and transferable to the study of packaging signals in other RNA viruses. Improved understanding of RNA packaging may lead to novel vaccine approaches or targets for antiviral drugs with broad spectrum activity.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Haydon, Professor Daniel and Logan, Grace and Cottam, Dr Eleanor and Tuthill, Dr Tobias
Authors: Logan, G., Newman, J., Wright, C. F., Lasecka-Dykes, L., Haydon, D. T., Cottam, E. M., and Tuthill, T. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
Journal Name:Journal of Virology
Publisher:American Society for Microbiology
ISSN:0022-538X
ISSN (Online):1098-5514
Published Online:18 October 2017
Copyright Holders:Copyright © 2017 Logan et al.
First Published:First published in Journal of Virology 92(1):e01159-17
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
632421An effective vaccination programme for the eradication of foot-and-mouth disease from IndiaRichard ReeveBiotechnology and Biological Sciences Research Council (BBSRC)BB/L004828/1 1805RI BIODIVERSITY ANIMAL HEALTH & COMPMED