Sheeppox virus kelch-like gene SPPV-019 affects virus virulence

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.