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Journal of Virology, August 2007, p. 8497-8506, Vol. 81, No. 16
0022-538X/07/$08.00+0     doi:10.1128/JVI.00340-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Guinea Pig-Adapted Foot-and-Mouth Disease Virus with Altered Receptor Recognition Can Productively Infect a Natural Host

José I. Núñez,^1,2, Nicolas Molina,² Eric Baranowski,^1, Esteban Domingo,¹ Stuart Clark,³ Alison Burman,³ Stephen Berryman,³ Terry Jackson,³ and Francisco Sobrino^1,2*

Centro de Biolgía Molecular Severo Ochoa (CSIC-UAM) Cantoblanco, 28049 Madrid, Spain,¹ Centro de Investigación en Sanidad Animal, INIA, Valdeolmos, 28130 Madrid, Spain,² Division of Microbiology, Institute for Animal Health, Pirbright, Surrey GU24 ONF, United Kingdom³

Received 15 February 2007/ Accepted 16 May 2007

We report that adaptation to infect the guinea pig did not modify the capacity of foot-and-mouth disease virus (FMDV) to kill suckling mice and to cause an acute and transmissible disease in the pig, an important natural host for this pathogen. Adaptive amino acid replacements (I₂₄₈T in 2C, Q₄₄R in 3A, and L₁₄₇P in VP1), selected upon serial passages of a type C FMDV isolated from swine (biological clone C-S8c1) in the guinea pig, were maintained after virus multiplication in swine and suckling mice. However, the adaptive replacement L₁₄₇P, next to the integrin-binding RGD motif at the GH loop in VP1, abolished growth of the virus in different established cell lines and modified its antigenicity. In contrast, primary bovine thyroid cell cultures could be productively infected by viruses with replacement L₁₄₇P, and this infection was inhibited by antibodies to vß6 and by an FMDV-derived RGD-containing peptide, suggesting that integrin vß6 may be used as a receptor for these mutants in the animal (porcine, guinea pig, and suckling mice) host. Substitution T₂₄₈N in 2C was not detectable in C-S8c1 but was present in a low proportion of the guinea pig-adapted virus. This substitution became rapidly dominant in the viral population after the reintroduction of the guinea pig-adapted virus into pigs. These observations illustrate how the appearance of minority variant viruses in an unnatural host can result in the dominance of these viruses on reinfection of the original host species.

Published ahead of print on 23 May 2007.

Present address: CReSA, UAB, 08193 Bellaterra, Barcelona, Spain.

Present address: INRA, UMR 1225, Ecole Nationale Vétérinaire de Toulouse, 31076 Toulouse, France.

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