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Journal of Virology, December 2008, p. 12232-12240, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01553-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Engineering Viable Foot-and-Mouth Disease Viruses with Increased Thermostability as a Step in the Development of Improved Vaccines {triangledown}

Roberto Mateo,{dagger} Eva Luna, Verónica Rincón, and Mauricio G. Mateu*

Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain

Received 23 July 2008/ Accepted 18 September 2008

We have rationally engineered foot-and-mouth disease virus to increase its stability against thermal dissociation into subunits without disrupting the many biological functions needed for its infectivity. Amino acid side chains located near the capsid intersubunit interfaces and either predicted or found to be dispensable for infectivity were replaced by others that could establish new disulfide bonds or electrostatic interactions between subunits. Two engineered viruses were normally infectious, genetically stable, and antigenically indistinguishable from the natural virus but showed substantially increased stability against irreversible dissociation. Electrostatic interactions mediated this stabilizing effect. For foot-and-mouth disease virus and other viruses, some evidence had suggested that an increase in virion stability could be linked to an impairment of infectivity. The results of the present study show, in fact, that virion thermostability against dissociation into subunits may not be selectively constrained by functional requirements for infectivity. The thermostable viruses obtained, and others similarly engineered, could be used for the production, using current procedures, of foot-and-mouth disease vaccines that are less dependent on a faultless cold chain. In addition, introduction of those stabilizing mutations in empty (nucleic acid-free) capsids could facilitate the production of infection-risk-free vaccines against the disease, one of the economically most important animal diseases worldwide.

* Corresponding author. Mailing address: Centro de Biologia Molecular "Severo Ochoa," Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid, Spain. Phone: 34-91-1964575. Fax: 34-91-1964420. E-mail: mgarcia{at}cbm.uam.es

{triangledown} Published ahead of print on 1 October 2008.

{dagger} Present address: Microbiology and Immunology Department, Fairchild Science Building, 299 Campus Drive, D-300 Stanford, CA 94305-5124.

Journal of Virology, December 2008, p. 12232-12240, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01553-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Luna, E., Rodriguez-Huete, A., Rincon, V., Mateo, R., Mateu, M. G. (2009). Systematic Study of the Genetic Response of a Variable Virus to the Introduction of Deleterious Mutations in a Functional Capsid Region. J. Virol. 83: 10140-10151 [Abstract] [Full Text]  


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