Thomzig Achim, Schulz-Schaeffer Walter, Wrede Arne, Wemheuer Wilhelm, Brenig Bertram, Kratzel Christine, Lemmer Karin, Beekes Michael
P24 Transmissible Spongiform Encephalopathies, Robert Koch-Institut, Berlin, Germany.
PLoS Pathog. 2007 May 25;3(5):e66. doi: 10.1371/journal.ppat.0030066.
Prion infectivity and its molecular marker, the pathological prion protein PrP(Sc), accumulate in the central nervous system and often also in lymphoid tissue of animals or humans affected by transmissible spongiform encephalopathies. Recently, PrP(Sc) was found in tissues previously considered not to be invaded by prions (e.g., skeletal muscles). Here, we address the question of whether prions target the skin and show widespread PrP(Sc) deposition in this organ in hamsters perorally or parenterally challenged with scrapie. In hamsters fed with scrapie, PrP(Sc) was detected before the onset of symptoms, but the bulk of skin-associated PrP(Sc) accumulated in the clinical phase. PrP(Sc) was localized in nerve fibres within the skin but not in keratinocytes, and the deposition of PrP(Sc) in skin showed no dependence from the route of infection and lymphotropic dissemination. The data indicated a neurally mediated centrifugal spread of prions to the skin. Furthermore, in a follow-up study, we examined sheep naturally infected with scrapie and detected PrP(Sc) by Western blotting in skin samples from two out of five animals. Our findings point to the skin as a potential reservoir of prions, which should be further investigated in relation to disease transmission.
朊病毒感染性及其分子标志物——病理性朊蛋白PrP(Sc)，在受传染性海绵状脑病影响的动物或人类的中枢神经系统中积累，并且通常也在淋巴组织中积累。最近，在以前被认为不会被朊病毒侵袭的组织（如骨骼肌）中发现了PrP(Sc)。在此，我们探讨朊病毒是否靶向皮肤，并在经口或经肠外途径感染羊瘙痒病的仓鼠的该器官中呈现广泛的PrP(Sc)沉积这一问题。在喂食羊瘙痒病的仓鼠中，在症状出现之前就检测到了PrP(Sc)，但与皮肤相关的PrP(Sc)大部分在临床阶段积累。PrP(Sc)定位于皮肤内的神经纤维中，而非角质形成细胞中，并且PrP(Sc)在皮肤中的沉积与感染途径和嗜淋巴扩散无关。数据表明朊病毒通过神经介导向皮肤进行离心扩散。此外，在一项后续研究中，我们检查了自然感染羊瘙痒病的绵羊，并通过蛋白质印迹法在五只动物中的两只的皮肤样本中检测到了PrP(Sc)。我们的研究结果表明皮肤是朊病毒的一个潜在储存库，应进一步研究其与疾病传播的关系。
