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Journal of Virology, March 2005, p. 3787-3796, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3787-3796.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The E2 Glycoprotein of Classical Swine Fever Virus Is a Virulence Determinant in Swine

G. R. Risatti ,^1,, M. V. Borca,^1,* G. F. Kutish,^1, Z. Lu,¹ L. G. Holinka,¹ R. A. French,^2, E. R. Tulman,^1, and D. L. Rock^1,

Plum Island Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Greenport, New York,¹ Department of Pathology and Veterinary Science, The University of Connecticut, Storrs, Connecticut²

Received 26 May 2004/ Accepted 9 November 2004

To identify genetic determinants of classical swine fever virus (CSFV) virulence and host range, chimeras of the highly pathogenic Brescia strain and the attenuated vaccine strain CS were constructed and evaluated for viral virulence in swine. Upon initial screening, only chimeras 138.8v and 337.14v, the only chimeras containing the E2 glycoprotein of CS, were attenuated in swine despite exhibiting unaltered growth characteristics in primary porcine macrophage cell cultures. Additional viral chimeras were constructed to confirm the role of E2 in virulence. Chimeric virus 319.1v, which contained only the CS E2 glycoprotein in the Brescia background, was markedly attenuated in pigs, exhibiting significantly decreased virus replication in tonsils, a transient viremia, limited generalization of infection, and decreased virus shedding. Chimeras encoding all Brescia structural proteins in a CS genetic background remained attenuated, indicating that additional mutations outside the structural region are important for CS vaccine virus attenuation. These results demonstrate that CS E2 alone is sufficient for attenuating Brescia, indicating a significant role for the CSFV E2 glycoprotein in swine virulence.

These authors contributed equally to the results presented in this report.

Present address: Department of Pathobiology and Veterinary Science and Center of Excellence for Vaccine Research, The University of Connecticut, Storrs, CT 06269-3089.

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