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Bovine papular stomatitis virus encodes a functionally distinct VEGF that binds both VEGFR-1 and VEGFR-2

Virus Research Unit, Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand

Correspondence
Lyn M. Wise
lyn.wise{at}stonebow.otago.ac.nz

Bovine papular stomatitis virus (BPSV), a member of the genus Parapoxvirus, causes proliferative dermatitis in cattle and humans. Other species of the genus cause similar lesions, the nature of which has been attributed, at least in part, to a viral-encoded vascular endothelial growth factor (VEGF) that induces vascularization and dermal oedema through VEGF receptor-2 (VEGFR-2). The results of this study showed that BPSV strain V660 encodes a novel VEGF and that the predicted BPSV protein showed only 33–52 % amino acid identity to VEGFs encoded by the other species of the genus. BPSV VEGF showed higher identity to mammalian VEGF-A (51 %) than the other parapoxviral VEGFs (31–46 %). Assays of the purified BPSV VEGF (BPSV_V660VEGF) demonstrated that it was also functionally more similar to VEGF-A, as it showed significant binding to VEGFR-1 and induced monocyte migration. Like VEGF-A and the other viral VEGFs, BPSV_V660VEGF bound VEGFR-2 with high affinity. Sequence analysis and structural modelling of BPSV_V660VEGF revealed specific residues, outside the known receptor-binding face, that are predicted either to influence VEGF structure or to mediate binding directly to the VEGFRs. These results indicate that BPSV_V660VEGF is a biologically active member of the VEGF family and that, via its interaction with VEGFR-2, it is likely to contribute to the proliferative and highly vascularized nature of BPSV lesions. This is also the first example of a viral VEGF acting via VEGFR-1 and influencing haematopoietic cell function. These data suggest that BPSV_V660VEGF is an evolutionary and functional intermediate between VEGF-A and the other parapoxviral VEGFs.

The GenBank/EMBL/DDBJ accession number for the sequence of the VEGF-like gene of BPSV strain V660 reported in this paper is AY513237.

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