The Role of Babesia bovis MSA-1 in Erythrocyte Invasion

描述(申请人提供)：Apicomplexan寄生虫属 巴贝斯虫和疟原虫感染成熟的红细胞并引起动物疾病 和人类。疫苗的主要策略是引导免疫反应 抗裂殖子表面蛋白，并阻止进入宿主红细胞。 虽然参与入侵的寄生虫蛋白已经被确定，但 这些蛋白质的功能和侵袭的分子机制是主要的 我们知识上的鸿沟。我建议用牛巴贝斯虫感染牛 以红细胞为模型研究裂殖子表面功能 入侵过程中的蛋白质。基于针对牛白僵菌抗体的能力 裂殖子表面抗原-1(MSA-1)防止裂殖子附着在 并在体外抑制红细胞侵袭，MSA-L已 推测是为了调节裂殖子与红细胞的附着。此外, 免疫牛中的突破性分离株表达MSA-1的等位基因变体， 建议在免疫压力下选择MSA-1变异体。因此，我是 有兴趣更好地了解马萨-L在有目标的入侵中的作用 为免疫定义保守的分子靶点。这项研究 这项提案中概述的将检验裂殖子表面 牛巴贝斯虫抗原-1(MSA-1)通过 与红细胞表面结合。这一假说将通过 以下具体目标：具体目标1：确定牛分枝杆菌MSA-1是否与 红血球表面。具体目标2：确定MSA-L是否受到抑制 表达会破坏寄生虫与红细胞的结合。具体目标3： 确定msa-L基因的破坏是否抑制寄生虫与And的结合 红细胞的侵袭。 这项研究的主要目的是增加我们对 巴贝斯虫侵袭红细胞的机制及其发育 一种用于研究其他Babesia1分子功能的系统 基因操纵。所获得的信息将扩大我们对 顶端复合体血寄生虫使用的比较入侵机制，包括 感染人类的巴贝斯虫和疟原虫。这个项目的结果是， 以及即将开发的转基因技术，将使我们能够 开始针对这些蛋白质中具有重要功能的区域 进一步研究。

DESCRIPTION (provided by applicant): Apicomplexan parasites in the genera Babesia and Plasmodium infect mature erythocytes and cause disease in animals and humans. A principal vaccine strategy is to direct immune responses against merozoite surface proteins and block entry into the host erythrocyte. While parasite proteins involved in invasion have been identified, the function of these proteins and the molecular mechanisms of invasion are major gaps in our knowledge. I propose to use Babesia bovis infection of bovine erythrocytes as a model to investigate the function of merozoite surface proteins in invasion. Based on the ability of antibodies against B. bovis merozoite surface antigen-1 (MSA-1) to prevent merozoite attachment to the erythrocyte and inhibit erythrocyte invasion in vitro, MSA-l has been postulated to mediate merozoite attachment to the erythrocyte. In addition, breakthrough isolates in vaccinated cattle express allelic variants of MSA-1, suggesting selection of MSA-1 variants under immune pressure. Therefore, I am interested in better understanding the role of MSA-l in invasion with the goal of defining conserved molecular targets for immunization. The research outlined in this proposal will test the hypothesis that merozoite surface antigen-1 (MSA-1) of Babesia bovis mediates erythrocyte invasion through binding to the erythrocyte surface. The hypothesis will be tested through the following specific aims: Specific aim 1: Determine if B. bovis MSA-1 binds to the erythrocyte surface. Specific aim 2: Determine if inhibition of MSA-l expression disrupts parasite binding to the erythrocyte. Specific aim 3: Determine if disruption of the msa-l gene inhibits parasite binding to and invasion of erythrocytes. The primary purposes of this research are to increase our understanding of the mechanisms of erythrocyte invasion used by babesial parasites, and to develop a system for investigating the function of other babesia1 molecules using genetic manipulation. The information obtained will expand our knowledge of comparative invasion mechanims used by apicomplexan hemoparasites, including Babesia and Plasmodium spp that infect humans. The results of this project, as well as the transfection techniques that will be developed, will allow us to begin targeting regions of functional significance in these proteins for further study.