Viral vascular endothelial growth factor plays a critical role in orf virus infection
Viral vascular endothelial growth factor plays a critical role in orf virus infection
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DOI：
10.1128/jvi.74.22.10699-10706.2000
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发表时间：
2000-11-01
影响因子：
5.4
通讯作者：
Mercer, AA
中科院分区：
文献类型：
--
作者：
Savory, LJ;Stacker, SA;Mercer, AA
副痘病毒感染引起增生性皮肤病变，其中广泛的毛细血管增生和扩张是突出的组织学特征。这种感染性表型可能与一种独特的病毒编码因子有关，这是血管内皮生长因子（VEGF）分子家族的一个独特的新成员。我们构建了一个重组的羊口疮病毒，其中VEGF样基因被破坏，并表明，该基因的失活导致三个VEGF的活动表达的亲本病毒的损失：血管内皮细胞的有丝分裂，诱导血管通透性，和激活的VEGF受体2。我们使用重组羊口疮病毒来评估在羊口疮病毒感染皮肤过程中病毒VEGF对血管反应的贡献。我们的研究结果表明，病毒VEGF，同时认识到一个独特的配置文件的已知的VEGF受体（受体2和neuropilin 1），是能够刺激一个显着的增殖血管在真皮下的感染部位。此外，数据表明，病毒VEGF参与促进表皮增殖的独特模式。功能性病毒VEGF的丧失导致病变的感染临床指征显著降低。然而，病毒复制在感染的早期阶段并没有受到损害，只有在后期才出现重组病毒的复制可能会减少。
Infection by the parapoxvirus orf virus causes proliferative skin lesions in which extensive capillary proliferation and dilation are prominent histological features. This infective phenotype may be linked to a unique virus-encoded factor, a distinctive new member of the vascular endothelial growth factor (VEGF) family of molecules. We constructed a recombinant orf virus in which the VEGF-like gene was disrupted and show that inactivation of this gene resulted in the loss of three VEGF activities expressed by the parent virus: mitogenesis of vascular endothelial cells, induction of vascular permeability, and activation of VEGF receptor 2. We used the recombinant orf virus to assess the contribution of the viral VEGF to the vascular response seen during orf virus infection of skin. Our results demonstrate that the viral VEGF, while recognizing a unique profile of the known VEGF receptors (receptor 2 and neuropilin 1), is able to stimulate a striking proliferation of blood vessels in the dermis underlying the site of infection. Furthermore, the data demonstrate that the viral VEGF participates in promoting a distinctive pattern of epidermal proliferation. Loss of a functional viral VEGF resulted in lesions with markedly reduced clinical indications of infection. However, viral replication in the early stages of infection was not impaired, and only at later times did it appear that replication of the recombinant virus might be reduced.