Virus-induced alterations of membrane lipids affect the incorporation of PrPSc into cells

Dana Avrahami, Yael Dayan-Amouyal, Saar Tal, Michal Mincberg, Claytus Davis, Oded Abramsky, Ruth Gabizon

    Research output: Contribution to journalArticlepeer-review

    7 Scopus citations


    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 naïve cells. Immunostaining of cells and immunoblotting of subcellular fractions using antibodies recognizing PrP and Lyso-Tracker, 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.

    Original languageEnglish
    Pages (from-to)2753-2762
    Number of pages10
    JournalJournal of Neuroscience Research
    Issue number12
    StatePublished - 8 Dec 2008


    • MVM
    • Prions
    • Rafts

    ASJC Scopus subject areas

    • Cellular and Molecular Neuroscience


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