Wise Lyn M, Savory Loreen J, Dryden Nicola H, Whelan Ellena M, Fleming Stephen B, Mercer Andrew A
Virus Research Unit, Department of Microbiology and Immunology, University of Otago, P.O. Box 56, Dunedin, New Zealand.
Virus Res. 2007 Sep;128(1-2):115-25. doi: 10.1016/j.virusres.2007.04.018. Epub 2007 May 23.
Orf virus infection causes a contagious pustular dermatitis characterized by extensive vascular changes that have been linked to a virally encoded vascular endothelial growth factor (VEGF). The VEGF genes of different strains of orf virus can vary extensively in amino acid sequence. Functional analyses of two major variant VEGF proteins derived from orf virus strains, NZ2 and NZ7, have revealed quantitative differences in biological activities and receptor binding specificities suggesting that these viral VEGFs could have different roles in the pathology of orf virus infection. In this study, we show that both orf virus strains express equivalent levels of the viral VEGF variants and during infection of sheep skin induce comparable levels of vascularization, edema, epidermal rete ridge and scab formation. Recombinants of orf virus NZ2 and NZ7 strains in which the variant VEGF genes were disrupted showed markedly reduced vascular changes and evidence of partially attenuated viral growth. These results demonstrate that despite substantial differences in sequence and biological activity in vitro, these virally expressed virulence factors are functionally equivalent in their natural host, contributing equally to orf virus pathology.
羊口疮病毒感染会引发一种传染性脓疱性皮炎，其特征为广泛的血管变化，这些变化与病毒编码的血管内皮生长因子（VEGF）有关。不同毒株的羊口疮病毒VEGF基因在氨基酸序列上可能存在很大差异。对源自羊口疮病毒毒株NZ2和NZ7的两种主要变体VEGF蛋白进行的功能分析显示，它们在生物活性和受体结合特异性方面存在数量差异，这表明这些病毒VEGF在羊口疮病毒感染的病理过程中可能具有不同作用。在本研究中，我们发现两种羊口疮病毒毒株表达的病毒VEGF变体水平相当，并且在感染绵羊皮肤期间，诱导的血管生成、水肿、表皮嵴和结痂形成水平相当。破坏了变体VEGF基因的羊口疮病毒NZ2和NZ7毒株的重组体显示血管变化明显减少，并且有病毒生长部分减弱的迹象。这些结果表明，尽管在体外序列和生物活性存在很大差异，但这些病毒表达的毒力因子在其天然宿主中功能等效，对羊口疮病毒病理过程的贡献相同。
