The defining characteristic of prion diseases is conversion of a cellular prion protein (PrP^C) to an abnormal prion protein (PrP^Sc). The exogenous attachment of PrP^Sc to the surface of a target cell is critical for infection. However, the initial interaction of PrP^Sc with the cell surface is poorly characterized. In the current study, we specifically focused on the association of PrP^Sc with cells during the early phase of infection, using an acute infection model. First, we treated mouse neuroblastoma N2a-58 cells with prion strain 22 L-infected brain homogenates and revealed that PrP^Sc was associated with membrane fractions within three hours, a short exposure time. These results were also observed in PrP^C-deficient hippocampus cell lines. We also demonstrate here that PrP^Sc from 22 L-infected brain homogenates was associated with lipid rafts during the early phase of infection. Furthermore, we revealed that DS500, a glycosaminoglycan mimetic, inhibited both the attachment of PrP^Sc to membrane fractions and subsequent prion transmission, suggesting that the early association of prions with cell surface is important for prion infection.

朊病毒疾病的定义特征是蜂窝朊病毒蛋白（PrP的转化^Ç）到异常朊病毒（PrP的^钪）。PrP ^Sc与靶细胞表面的外源性附着对于感染至关重要。然而，PrP ^Sc与细胞表面的初始相互作用的特征很差。在当前的研究中，我们使用急性感染模型特别关注感染早期阶段PrP ^Sc与细胞的关联。首先，我们用朊病毒株 22 L 感染的脑匀浆处理小鼠神经母细胞瘤 N2a-58 细胞，发现 PrP ^Sc在三小时内与膜组分相关联，暴露时间很短。在PrP ^C缺陷的海马细胞系中也观察到这些结果。我们还在这里证明，在感染的早期阶段，来自 22 个 L 感染的脑匀浆的PrP ^Sc与脂筏有关。此外，我们发现 DS500，一种糖胺聚糖模拟物，抑制了 PrP ^Sc与膜组分的附着和随后的朊病毒传播，这表明朊病毒与细胞表面的早期关联对于朊病毒感染很重要。