Stumpf M P, Krakauer D C
The Wellcome Trust Centre for the Epidemiology of Infectious Disease, Department of Zoology, South Parks Road, Oxford OX1 3PS, United Kingdom.
Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10573-7. doi: 10.1073/pnas.180317097.
We present a theoretical framework that enables us to dissect out the parametric dependencies of the pathogenesis of prion diseases. We are able to determine the influence of both host-dependent factors (connectivity, cell density, protein synthesis rate, and cell death) and strain-dependent factors (cell tropism, virulence, and replication rate). We use a model based on a linked system of differential equations on a lattice to explore how the regional distribution of central nervous system pathology in Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia relates to each of these factors. The model then is used to make qualitative predictions about the pathology for two possible hypothetical triggers of neuronal loss in prion diseases. Pathological progression in overexpressing mouse models has been shown to depend on the site of initial infection. The model allows us to compare the pathologies resulting from different inoculation routes.
我们提出了一个理论框架,使我们能够剖析朊病毒疾病发病机制的参数依赖性。我们能够确定宿主依赖性因素(连接性、细胞密度、蛋白质合成速率和细胞死亡)和毒株依赖性因素(细胞嗜性、毒力和复制速率)的影响。我们使用基于晶格上微分方程链接系统的模型,来探究克雅氏病、格斯特曼-施特劳斯勒-谢inker综合征和致死性家族性失眠症中中枢神经系统病理学的区域分布与这些因素中的每一个是如何相关的。然后,该模型用于对朊病毒疾病中两种可能的神经元损失假设触发因素的病理学进行定性预测。在过表达小鼠模型中的病理进展已被证明取决于初始感染部位。该模型使我们能够比较不同接种途径所导致的病理学情况。