Tawe W, Pearlman E, Unnasch T R, Lustigman S
Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
Mol Biochem Parasitol. 2000 Jul;109(2):91-9. doi: 10.1016/s0166-6851(00)00231-0.
Although the mechanisms underlying the host inflammatory response in ocular onchocerciasis have been examined, the role of particular parasite proteins in this process remains largely unexplored. Recently, it was found that one of the most abundant expressed sequence tags in Onchocerca volvulus infective larvae encoded a protein with similarities to a component of vespid venom. This clone was designated O. volvulus Activation associated Secreted Protein -1 (Ov-asp-1). We report the characterization of three members of a family of proteins, designated the Ov-ASP family, of which Ov-ASP-1 is a member. Sequence based and phylogenetic analyses suggest that these proteins form a filarial specific protein family related to both the vespid venom antigen 5 and the vertebrate CRISP/Tpx family of proteins. The three members of the Ov-ASP family exhibit distinct patterns of expression in the life cycle of O. volvulus. Genomic Southern blot analyses indicate that several genes encoding sequences related to the Ov-asp family are present in the genome of O. volvulus. Recombinant proteins expressed from full length cDNAs encoding two members of the Ov-asp family were found to induce an angiogenic response after injection into corneas of naive mice, and vessel formation was associated with only minor inflammatory cell infiltration. These data suggest that Ov-ASP proteins may directly induce an angiogenic response and may therefore contribute to corneal neovascularization in onchocercal keratitis.
尽管已经对盘尾丝虫性眼病中宿主炎症反应的潜在机制进行了研究,但特定寄生虫蛋白在此过程中的作用在很大程度上仍未得到探索。最近,人们发现盘尾丝虫感染性幼虫中表达最丰富的序列标签之一编码一种与黄蜂毒液成分相似的蛋白质。这个克隆被命名为盘尾丝虫激活相关分泌蛋白-1(Ov-asp-1)。我们报告了一个蛋白质家族(命名为Ov-ASP家族)中三个成员的特性,其中Ov-ASP-1是该家族的一员。基于序列和系统发育分析表明,这些蛋白质形成了一个丝虫特异性蛋白家族,与黄蜂毒液抗原5和脊椎动物CRISP/Tpx蛋白家族都有关。Ov-ASP家族的三个成员在盘尾丝虫的生命周期中表现出不同的表达模式。基因组Southern印迹分析表明,盘尾丝虫基因组中存在几个编码与Ov-asp家族相关序列的基因。将编码Ov-asp家族两个成员的全长cDNA表达的重组蛋白注射到未感染小鼠的角膜后,发现可诱导血管生成反应,并且血管形成仅伴有轻微的炎性细胞浸润。这些数据表明,Ov-ASP蛋白可能直接诱导血管生成反应,因此可能导致盘尾丝虫性角膜炎中的角膜新生血管形成。