Studies on Cryptosporidium parvum Type 1

描述(由申请人提供)：这是一份修订后的建议书 (R01AI150471-01)回应PA 99-124。这个项目的目标是 微小隐孢子虫1型最多的综合特性 普通人群和人群中人类隐孢子虫病的共同病原体 得了艾滋病。因为直到最近，1型C.parvum还不能在 实验室，这一亚群很少被研究，而且仍然很差 特色化的。因此，小牛繁殖型的表型特性 2个卵囊外推到整个物种。根据重要的 微小丙型隐孢子虫病对公共卫生的重要性 这一建议的重点有两个：1)广泛地表征微小隐孢子虫 关于遗传型和表型特性以及其寿命的类型1 循环和与宿主的相互作用，以及(2)比较微小弧菌1型和 类型2，目的是更好地了解微小隐孢子虫 以及由这种寄生虫引起的疾病。A的最新发展 适合1型和2型繁殖的灵知生猪模型将 促进对几种1型分离株的研究和比较 来自同一宿主的两种类型的标准细小弧菌分离物。 在混合感染中，1型和2型分离株的相互作用也将是 在猪模型中进行了研究。这项研究中包括的1型分离株将起源于 来自不同地理区域的慢性和急性感染。这个 研究包括三个具体目标：第一个目标是综合分析 在10个1型微小隐孢子虫分离株中。第二个目标是寄主--寄生虫 类型1和类型2分离株的相互作用将使用猪模型进行比较 和细胞培养模型。第三个目的是调查遗传的程度 微小隐孢子虫在两种类型内和之间的变异和交换 确定它们属于一个还是两个物种。

DESCRIPTION (Provided by the applicant): This is a revised proposal (R01AI150471-01) in response to PA 99-124. The goal of this project is a comprehensive characterization of Cryptosporidium parvum type 1, the most common agent of human cryptosporidiosis in the general population and in people with AIDS. Because until recently type 1 C. parvum could not be propagated in the laboratory, this subgroup is rarely studied and remains poorly characterized. As a consequence, phenotypic properties of calf-propagated type 2 oocysts are extrapolated to the whole species. In light of the significant public health importance of cryptosporidiosis caused by type 1 C. parvum, the emphasis of this proposal is twofold: 1) to extensively characterize C. parvum type 1 with respect to genotypic and phenotypic properties, as well as its life cycle and interaction with the host, and (2) to compare C. parvum type 1 and type 2 with the aim of gaining a better understanding of the species C. parvum and the disease caused by this parasite. The recent development of a gnotobiotic pig model suitable for propagation of type 1 and type 2 will facilitate the study of several type 1 isolates and the comparison of standardized C. parvum isolates of both types originating from the same host. The interaction of type 1 and type 2 isolates in mixed infections will also be studied in the pig model. Type 1 isolates included in this study will originate from chronic and acute infections and from different geographical areas. The study includes three specific aims: the first aim is a comprehensive analysis of ten type 1 C. parvum isolates. In the second aim the host-parasite interaction of type 1 and type 2 isolates will be compared using the pig model and cell culture models. The third aim investigates the extent of genetic variation and exchange within and between the two types of C. parvum to determine whether they belong to one or two species.