The Role of Babesia bovis MSA-1 in Erythrocyte Invasion

牛巴贝虫 MSA-1 在红细胞侵袭中的作用

• 批准号: 6750121
• 负责人: Tanya LeRoith
• 金额: $ 8.24万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6750121
• 关键词: Babesia; antibody titering; antigen antibody reaction; antisense nucleic acid; babesiosis; binding proteins; biological models; blocking antibody; cell line; cell sorting; cow; erythrocyte membrane; gene induction /repression; gene targeting; genetic translation; host organism interaction; immune adherence reaction; immunocytochemistry; intracellular parasitism; molecular cloning; plasmids; protein biosynthesis; protein structure function; protozoal antigen; site directed mutagenesis; surface antigens; transfection /expression vector

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.

描述（申请人提供）：属中的Apicomplexan寄生虫 巴贝斯和疟原虫感染成熟的红细胞，并引起动物疾病 和人类。 主要疫苗策略是指导免疫反应 针对梅罗罗派表面蛋白，并阻止进入宿主红细胞。 尽管已经确定了参与侵袭的寄生虫蛋白，但 这些蛋白质的功能和侵袭的分子机制是主要的 我们的知识差距。 我建议使用牛的牛babesia牛感染 红细胞作为研究梅罗洛岩表面功能的模型 入侵中的蛋白质。 基于抗B. B. b. b. b. Merozoite表面抗原-1（MSA-1），以防止梅罗祖岩附着 红细胞和抑制性红细胞在体外，MSA-L已 假定是为了介导梅洛祖岩附着在红细胞上。 此外， 接种牛的突破性分离株Express Express等位基因变体的MSA-1， 建议在免疫压力下选择MSA-1变体。 因此，我是 有兴趣更好地了解MSA-L在入侵中的作用 定义保守的分子靶标进行免疫。 研究 该提案中概述将检验梅罗洛唑表面的假设 Babesia Bovis的抗原1（MSA-1）通过 与红细胞表面结合。 该假设将通过 以下特定目的：具体目的1：确定B. b. Bovis msa-1是否与 红细胞表面。 特定目标2：确定抑制MSA-L 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和 红细胞的入侵。 这项研究的主要目的是增加我们对 巴布西寄生虫使用的红细胞侵袭机制，并发展 一种用于研究其他Babesia1分子功能的系统 基因操纵。 获得的信息将扩大我们对 APICOMPLEXAN造血物使用的比较浸润机制，包括 贝贝西亚和疟原虫感染人类。 这个项目的结果， 以及将要开发的转染技术，将使我们 开始针对这些蛋白质功能显着性区域的目标 进一步研究。