HOMOLOGS OF VASCULAR ENDOTHELIAL GROWTH-FACTOR ARE ENCODED BY THE POXVIRUS ORF VIRUS

A gene encoding a polypeptide with homology to mammalian vascular endo thelial growth factors (VEGFs) has been discovered in the genome of or f virus (OV), a parapoxvirus that affects sheep and goats and, occasio nally, humans. The gene is transcribed abundantly early in infection a nd is found immediately outside the inverted terminal repeat at the ri ght end of the genome. In the NZ2 strain of OV (OV NZ2), the gene enco des a polypeptide with a molecular size of 14.7 kDa, while in another strain, OV NZ7, there is a variant gene that encodes a polypeptide of 16 kDa. The OV NZ2 and OV NZ7 polypeptides show 22 to 27% and 16 to 23 % identity, respectively, to the mammalian VEGFs. The viral polypeptid es are only 41.1% identical to each other, and there is little homolog y between the two genes at the nucleotide level. Another unusual featu re of these genes is their G+C content, particularly that of OV NZ7. I n a genome that is otherwise 63% G+C, the OV NZ2 gene is 57.2% G+C and the OV NZ7 gene is 39.7% G+C. The OV NZ2 gene, but not the OV NZ7 gen e, is homologous to the mammalian VEGF genes at the DNA level, suggest ing that the gene has been acquired from a mammalian host and is under going genetic drift. The lesions induced in sheep and humans after inf ection with OV show extensive dermal vascular endothelial proliferatio n and dilatation, and it is likely that this is a direct effect of the expression of the VEGF-like gene.