PRION STRAIN TARGETING AND COMPETITION IN THE CENTRAL NERVOUS SYSTEM

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项建议的目的是确定Pron感染对随后接种的第二Pron菌株复制的影响。用长潜伏期的Prion菌株预先接种啮齿动物可以延迟潜伏期或阻断随后接种(即重复感染)的短潜伏期Prion菌株，然而，中枢神经系统中发生Prion菌株选择的位置和细胞类型尚不清楚。对抑制重叠感染的病毒株复制的机制的研究可能有助于鉴定与病毒复制有关的宿主因子。需要检验的假设是，神经元的普里恩感染抑制了随后的普里恩感染和/或另一株普鲁恩病毒的复制。为了验证这一假说，将使用Pron株靶向和竞争的坐骨神经模型。在这种普恩病毒病模型中，普恩病毒沿着三条运动脊髓束被输送到大脑。在大鼠坐骨神经接种短潜伏期高TME菌株(HY TME)前120天，用长潜伏期金黄地鼠适应TME嗜睡株(DY TME)接种坐骨神经，可阻断HY TME，导致DY TME。Prion菌株选择的坐骨神经模型可以帮助识别Pron菌株选择所涉及的区域和细胞类型。

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.