1887

Abstract

(BPSV), a member of the genus , 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 (BPSVVEGF) 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, BPSVVEGF bound VEGFR-2 with high affinity. Sequence analysis and structural modelling of BPSVVEGF 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 BPSVVEGF 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 BPSVVEGF is an evolutionary and functional intermediate between VEGF-A and the other parapoxviral VEGFs.

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2007-03-01
2019-11-12
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