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首页> 外文期刊>The European Journal of Neuroscience >Clearance and prevention of prion infection in cell culture by anti-PrP antibodies.
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Clearance and prevention of prion infection in cell culture by anti-PrP antibodies.

机译：抗PrP抗体清除和预防细胞培养中的ion病毒感染。

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摘要

Prion diseases are transmissible and invariably fatal neurodegenerative disorders associated with a conformational transformation of the cellular prion protein (PrP(C)) into a self-replicating and proteinase K (PK)-resistant conformer, scrapie PrP (PrP(Sc)). Humoral immunity may significantly prolong the incubation period and even prevent disease in murine models of prionoses. However, the mechanism(s) of action of anti-PrP monoclonal antibodies (Mabs) remain(s) obscure. The murine neuroblastoma N2a cell line, infected with the 22L mouse-adapted scrapie strain, was used to screen a large library of Mabs with similar binding affinities to PrP, to identify those antibodies which could clear established infection and/or prevent infection de novo. Three Mabs were found capable of complete and persistent clearing of already-infected N2a cells of PrP(Sc). These antibodies were 6D11 (generated to PK-resistant PrP(Sc) and detecting PrP residues 93-109), and 7H6 and 7A12, which were raised against recombinant PrP and react with neighbouring epitopes of PrP residues 130-140 and 143-155, respectively. Mabs were found to interact with PrP(Sc) formation both on the cell surface and after internalization in the cytosol. Treatment with Mabs was not associated with toxicity nor did it result in decreased expression of PrP(C). Both preincubation of N2a cells with Mabs prior to exposure to 22L inoculum and preincubation of the inoculum with Mabs prior to infecting N2a cells resulted in a significant reduction in PrP(Sc) levels. Information provided in these studies is important for the rational design of humoral immune therapy for prion infection in animals and eventually in humans.
机译：on病毒疾病是与细胞病毒蛋白（PrP（C））构象转化为自复制抗蛋白酶K（PK）的顺应性构象，痒痒病PrP（PrP（Sc））相关的可传播的致命性神经退行性疾病。体液免疫可以显着延长潜伏期，甚至可以预防鼠类小鼠的ion病毒疾病。然而，抗PrP单克隆抗体（Mab）的作用机制仍然不清楚。用感染22L小鼠的瘙痒病菌株感染的鼠神经母细胞瘤N2a细胞系，用于筛选与PrP具有相似结合亲和力的大型单克隆抗体文库，以鉴定可以清除既定感染和/或从头预防感染的抗体。发现三个单克隆抗体能够完全和持久清除已感染的PrP（Sc）N2a细胞。这些抗体是6D11（针对PK抗性PrP（Sc）生成并检测PrP残基93-109），7H6和7A12，它们针对重组PrP产生并与PrP残基130-140和143-155的邻近表位反应，分别。发现单克隆抗体与PrP（Sc）的形成都在细胞表面和内化在细胞质中后相互作用。用单克隆抗体治疗与毒性无关，也不会导致PrP（C）表达降低。在暴露于22L接种物之前，用Mabs对N2a细胞进行预培养，然后在感染N2a细胞之前，用Mabs对接种物进行预培养，都导致PrP（Sc）水平显着降低。这些研究中提供的信息对于合理设计动物和最终人类病毒感染的体液免疫疗法很重要。

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