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Journal of Virology, October 2007, p. 11392-11401, Vol. 81, No. 20
0022-538X/07/$08.00+0     doi:10.1128/JVI.01093-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Sheeppox Virus Kelch-Like Gene SPPV-019 Affects Virus Virulence{triangledown}

C. A. Balinsky,1,2,3 G. Delhon,3,4,5 C. L. Afonso,3,6 G. R. Risatti,2,3 M. V. Borca,3 R. A. French,2 E. R. Tulman,1,2,3 S. J. Geary,1,2 and D. L. Rock3,5*

Center of Excellence for Vaccine Research, University of Connecticut, Storrs, Connecticut 06269,1 Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, Connecticut 06269,2 Plum Island Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Greenport, New York 11944,3 Area of Virology, School of Veterinary Sciences, University of Buenos Aires, 1427 Buenos Aires, Argentina,4 Department of Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana, Illinois 61802,5 Southeast Poultry Research Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Athens, Georgia 306056

Received 21 May 2007/ Accepted 30 July 2007

Sheeppox virus (SPPV), a member of the Capripoxvirus genus of the Poxviridae, is the etiologic agent of a significant disease of sheep in the developing world. Genomic analysis of pathogenic and vaccine capripoxviruses identified genes with potential roles in virulence and host range, including three genes with similarity to kelch-like genes of other poxviruses and eukaryotes. Here, a mutant SPPV with a deletion in the SPPV-019 kelch-like gene, {Delta}KLP, was derived from the pathogenic strain SPPV-SA. {Delta}KLP exhibited in vitro growth characteristics similar to those of SPPV-SA and revertant virus (RvKLP). {Delta}KLP-infected cells exhibited a reduction in Ca2+-independent cell adhesion, suggesting that SPPV-019 may modulate cellular adhesion. When inoculated in sheep by the intranasal or intradermal routes, {Delta}KLP was markedly attenuated, since all {Delta}KLP-infected lambs survived infection. In contrast, SPPV-SA and RvKLP induced mortality approaching 100%. Lambs inoculated with {Delta}KLP exhibited marked reduction or delay in fever response, gross lesions, viremia, and virus shedding compared to parental and revertant viruses. Together, these findings indicate that SPPV-019 is a significant SPPV virulence determinant in sheep.


* Corresponding author. Mailing address: 2522 Veterinary Medicine Basic Science Building, MC-002, 2001 S. Lincoln Ave., Urbana, IL 61802. Phone: (217) 244-0533. Fax: (217) 244-7421. E-mail: dlrock{at}uiuc.edu

{triangledown} Published ahead of print on 8 April 2007.


Journal of Virology, October 2007, p. 11392-11401, Vol. 81, No. 20
0022-538X/07/$08.00+0     doi:10.1128/JVI.01093-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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