Archer Fabienne, Bachelin Corinne, Andreoletti Olivier, Besnard Nathalie, Perrot Gregory, Langevin Christelle, Le Dur Annick, Vilette Didier, Baron-Van Evercooren Anne, Vilotte Jean-Luc, Laude Hubert
Unité de Virologie Immunologie Moléculaires, INRA, Jouy-en-Josas, France.
J Virol. 2004 Jan;78(1):482-90. doi: 10.1128/jvi.78.1.482-490.2004.
Transmissible spongiform encephalopathies arise as a consequence of infection of the central nervous system (CNS) by prions. Spreading of the infectious agent through the peripheral nervous system (PNS) may represent a crucial step toward CNS neuroinvasion, but the modalities of this process have yet to be clarified. Here we provide further evidence that PNS glial cells are likely targets for infection by prions. Glial cell clones originating from dorsal root ganglia of transgenic mice expressing ovine PrP (tgOv) and simian virus 40 T antigen were found to be readily infectible by sheep scrapie agent. This led us to establish two stable cell lines that exhibited features of Schwann cells. These cells were shown to sustain an efficient and stable replication of sheep prion based on the high level of accumulation of abnormal PrP and infectivity in exposed cultures. We also provide evidence for abnormal PrP deposition in peripheral neuroglial cells from scrapie-infected tgOv mice and sheep. These findings have potential implications in terms of designing new cell systems permissive to prions and of peripheral pathobiology of prion infections.
传染性海绵状脑病是由朊病毒感染中枢神经系统（CNS）引起的。感染因子通过外周神经系统（PNS）传播可能是CNS神经侵袭的关键步骤，但这一过程的方式尚待阐明。在此，我们提供进一步证据表明，PNS神经胶质细胞可能是朊病毒感染的靶标。发现源自表达羊PrP（tgOv）和猿猴病毒40 T抗原的转基因小鼠背根神经节的神经胶质细胞克隆很容易被羊瘙痒病病原体感染。这使我们建立了两个具有施万细胞特征的稳定细胞系。基于暴露培养物中异常PrP的高水平积累和传染性，这些细胞被证明能够维持羊朊病毒高效且稳定的复制。我们还提供了来自瘙痒病感染的tgOv小鼠和绵羊的外周神经胶质细胞中异常PrP沉积的证据。这些发现对于设计允许朊病毒生长的新细胞系统以及朊病毒感染的外周病理生物学具有潜在意义。
