PRION STRAIN TARGETING AND COMPETITION IN THE CENTRAL NERVOUS SYSTEM

中枢神经系统中朊病毒株的靶向和竞争

• 批准号: 7959390
• 负责人: Jason C Bartz
• 金额: $ 6.49万
• 依托单位: UNIVERSITY OF NEBRASKA LINCOLN
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959390
• 关键词: Area; Brain; Computer Retrieval of Information on Scientific Projects Database; Funding; Goals; Grant; Hamsters; Infection; Institution; Integration Host Factors; Investigation; Lead; Location; Modeling; Motor; Nebraska; Neuraxis; Neurons; Prion Diseases; Prions; Research; Research Personnel; Resources; Rodent; Source; Testing; United States National Institutes of Health; cell type; sciatic nerve; spinal tract; virology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this proposal is to identify the effects of prion infection on replication of a subsequently inoculated second prion strain. Prior inoculation of rodents with a long incubation prion strain can delay the incubation period or block a subsequently inoculated (i.e. superinfected) short incubation prion strain, however, the location and cell types in the CNS where prion strain selection occur are not known. Investigation of the mechanisms responsible for the inhibition of the superinfected prion strain replication may lead to identification of host factors involved in prion replication. The hypothesis to be tested is that prion infection of neurons inhibits subsequent prion infection and/or replication of another prion strain. To test this hypothesis, the sciatic nerve model of prion strain targeting and competition will be utilized. In this model of prion disease, prions are transported to the brain along three motor spinal tracts. Inoculation of the sciatic nerve with the long incubation period drowsy strain of hamster-adapted TME (DY TME) 120 days prior to sciatic nerve inoculation with the short incubation period hyper TME (HY TME) strain can block HY TME and results in DY TME. The sciatic nerve model of prion strain selection can facilitate the identification of the areas and cell types involved in prion strain selection.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 该提案的目的是确定朊病毒感染对随后接种的第二朊病毒株复制的影响。 先前给啮齿类动物接种长孵化朊病毒株可以延迟潜伏期或阻断随后接种（即重复感染）的短孵化朊病毒株，然而，中枢神经系统中朊病毒株选择发生的位置和细胞类型尚不清楚。 对抑制重复感染的朊病毒株复制的机制的研究可能有助于鉴定参与朊病毒复制的宿主因子。 要测试的假设是神经元的朊病毒感染抑制随后的朊病毒感染和/或另一种朊病毒株的复制。 为了检验这一假设，将利用朊病毒菌株靶向和竞争的坐骨神经模型。 在这种朊病毒疾病模型中，朊病毒沿着三个运动脊髓束转运到大脑。 在坐骨神经接种短潜伏期超级 TME (HY TME) 菌株之前 120 天，用仓鼠适应 TME (DY TME) 的长潜伏期昏昏欲睡菌株接种坐骨神经，可以阻断 HY TME 并导致 DY TME。 朊病毒株选择的坐骨神经模型有助于识别朊病毒株选择所涉及的区域和细胞类型。