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Journal of Virology, April 2001, p. 3977-3983, Vol. 75, No. 8
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.8.3977-3983.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

A Single Amino Acid Substitution in Nonstructural Protein 3A Can Mediate Adaptation of Foot-and-Mouth Disease Virus to the Guinea Pig

Jose Ignacio Núñez,1,2 Eric Baranowski,1 Nicolas Molina,1,dagger Carmen M. Ruiz-Jarabo,1 Carmen Sánchez,2 Esteban Domingo,1 and Francisco Sobrino1,2,*

Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma de Madrid, 28049 Madrid,1 and CISA-INIA, Valdeolmos, 28130 Madrid,2 Spain

Received 31 July 2000/Accepted 8 January 2001

The genetic changes selected during the adaptation of a clonal population of foot-and-mouth disease virus (FMDV) to the guinea pig have been analyzed. FMDV clone C-S8c1 was adapted to the guinea pig by serial passage in the animals until secondary lesions were observed. Analysis of the virus directly recovered from the lesions developed by the animals revealed the selection of variants with two amino acid substitutions in nonstructural proteins, I248right-arrowT in 2C and Q44right-arrowR in 3A. On further passages, an additional mutation, L147right-arrowP, was selected in an important antigenic site located in the G-H loop of capsid protein VP1. The amino acid substitution Q44right-arrowR in 3A, either alone or in combination with the replacement I248right-arrowT in 2C, was sufficient to give FMDV the ability to produce lesions. This was shown by using infectious transcripts which generated chimeric viruses with the relevant amino acid substitutions. Clinical symptoms produced by the artificial chimeras were similar to those produced by the naturally adapted virus. These results obtained with FMDV imply that one or very few replacements in nonstructural viral proteins, which should be within reach of the mutant spectra of replicating viral quasispecies, may result in adaptation of a virus to a new animal host.

* Corresponding author. Mailing address: Centro de Biología Molecular "Severo Ochoa", Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain. Phone: 34-91-3978307. Fax: 34-91-3974799. E-mail: fsobrino{at}cnb.uam.es.

dagger Permanent address: Department of Biology, Universidad del Atlántico, Barranquilla, Colombia.

Journal of Virology, April 2001, p. 3977-3983, Vol. 75, No. 8
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.8.3977-3983.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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