Dextran sulphate inhibits an association of prions with plasma membrane at the early phase of infection

The defining characteristic of prion diseases is conversion of a cellular prion protein (PrPC) to an abnormal prion protein (PrPSc). The exogenous attachment of PrPSc to the surface of a target cell is critical for infection. However, the initial interaction of PrPSc with the cell surface is poorly characterized. In the current study, we specifically focused on the association of PrPSc 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 PrPSc was associated with membrane fractions within three hours, a short exposure time. These results were also observed in PrPC-deficient hippocampus cell lines. We also demonstrate here that PrPSc 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. (C) 2021 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.

Automated summary

The study found that in the early stages of prion disease infection, PrPSc is associated with membrane fractions and lipid rafts. Use of DS500 can inhibit the attachment of PrPSc and subsequent prion transmission. This suggests that the early association of PrPSc with the cell surface is crucial for prion infection.