Virus-induced alterations of membrane lipids affect the incorporation of PrP Sc into cells
| Autor: | Dana Avrahami, Claytus Davis, Saar Tal, Yael Dayan-Amouyal, Oded Abramsky, Ruth Gabizon, Michal Mincberg |
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| Rok vydání: | 2008 |
| Předmět: |
PrPSc Proteins
viruses animal diseases media_common.quotation_subject Membrane lipids Scrapie Virus Prion Diseases Cellular and Molecular Neuroscience chemistry.chemical_compound Membrane Lipids Mice Cricetinae Animals Internalization Cells Cultured media_common biology Mesocricetus Cell Membrane Brain Glycosphingolipid biology.organism_classification nervous system diseases Cell biology Biochemistry chemistry biology.protein Minute Virus of Mice Antibody Minute virus of mice Immunostaining |
| Zdroj: | Journal of neuroscience research. 86(12) |
| ISSN: | 1097-4547 |
| Popis: | Prion diseases are fatal neurodegenerative disorders characterized by long incubation periods. To investigate whether concurrent diseases can modify the clinical outcome of prion-affected subjects, we tested the effect of viral infection on the binding and internalization of PrPSc, essential steps of prion propagation. To this effect, we added scrapie brain homogenate or purified PrPSc to fibroblasts previously infected with minute virus of mice (MVM), a mouse parvovirus. We show here that the rate of incorporation of PrPSc into MVM-infected cells was significantly higher than that observed for naive cells. Immunostaining of cells and immunoblotting of subcellular fractions using antibodies recognizing PrP and LysoTracker, a lysosomal marker, revealed that in both control and MVM-infected cells the incorporated PrPSc was associated mostly with lysosomes. Interestingly, floatation gradient analysis revealed that the majority of the PrPSc internalized into MVM-infected cells shifted toward raft-containing low-density fractions. Concomitantly, the MVM-infected cells demonstrated increased levels of the glycosphingolipid GM1 (an essential raft lipid component) throughout the gradient and a shift in caveolin 1 (a raft protein marker) toward lighter membrane fractions compared with noninfected cells. Our results suggest that the effect of viral infection on membrane lipid composition may promote the incorporation of exogenous PrPSc into rafts. Importantly, membrane rafts are believed to be the conversion site of PrPC to PrPSc; therefore, the association of exogenous PrPSc with such membrane microdomains may facilitate prion infection. © 2008 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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