Friedrich-Loeffler-Institut, Institute of Novel and Emerging Infectious Diseases , Greifswald , Germany.
Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut , Greifswald , Germany.
Prion. 2019 Jan;13(1):160-172. doi: 10.1080/19336896.2019.1651180.
After the discovery of two atypical bovine spongiform encephalopathy (BSE) forms in France and Italy designated H- and L-BSE, the question arose whether these new forms differed from classical BSE (C-BSE) in their pathogenesis. Samples collected from cattle in the clinical stage of BSE during an intracranial challenge study with L- and H-BSE were analysed using biochemical and histological methods as well as in a transgenic mouse bioassay. Our results generally confirmed what had been described for C-BSE to be true also for both atypical BSE forms, namely the restriction of the pathological prion protein (PrP) and BSE infectivity to the nervous system. However, analysis of samples collected under identical conditions from both atypical H- and L-BSE forms allowed us a more precise assessment of the grade of involvement of different tissues during the clinical end stage of disease as compared to C-BSE. One important feature is the involvement of the peripheral nervous and musculoskeletal tissues in both L-BSE and H-BSE affected cattle. We were, however, able to show that in H-BSE cases, the PrP depositions in the central and peripheral nervous system are dominated by a glial pattern, whereas a neuronal deposition pattern dominates in L-BSE cases, indicating differences in the cellular and topical tropism of both atypical BSE forms. As a consequence of this cell tropism, H-BSE seems to spread more rapidly from the CNS into the periphery via the glial cell system such as Schwann cells, as opposed to L-BSE which is mostly propagated via neuronal cells.
在法国和意大利发现了两种非典型牛海绵状脑病（BSE）形式，分别命名为 H 型和 L 型 BSE 后，人们开始怀疑这些新形式在发病机制上是否与经典 BSE（C-BSE）有所不同。在使用 L 型和 H 型 BSE 进行颅内攻毒研究的 BSE 临床阶段，从牛身上采集的样本使用生化和组织学方法以及转基因小鼠生物测定进行了分析。我们的结果普遍证实了以前对 C-BSE 的描述也适用于这两种非典型 BSE 形式，即病理性朊病毒蛋白（PrP）和 BSE 感染局限于神经系统。然而，在相同条件下从两种非典型 H 型和 L 型 BSE 形式采集的样本分析使我们能够更准确地评估与 C-BSE 相比，疾病临床终末期不同组织的受累程度。一个重要特征是 L-BSE 和 H-BSE 受感染牛的周围神经和肌肉骨骼组织受累。然而，我们能够表明，在 H-BSE 病例中，中枢和周围神经系统中的 PrP 沉积主要由神经胶质模式主导，而在 L-BSE 病例中则由神经元沉积模式主导，表明这两种非典型 BSE 形式在细胞和局部嗜性上存在差异。由于这种细胞嗜性，H-BSE 似乎通过神经胶质细胞系统（如施万细胞）从中枢神经系统更快地传播到外周，而 L-BSE 主要通过神经元细胞传播。
