NR AWIT
AU Leblanc,P.; Alais,S.; Porto-Carreiro,I.; Lehmann,S.; Grassi,J.; Raposo,G.; Darlix,J.L.
TI Retrovirus infection strongly enhances scrapie infectivity release in cell culture
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions S-15
PT Konferenz-Poster
AB Prion diseases are neurodegenerative disorders associated in most cases with the accumulation in the central nervous system of PrPsc, a partially protease-resistant isoform of the cellular prion protein PrPc. PrPsc is thought to be the causative agent of Transmissible Spongiform Encephalopathies (TSEs). The prion proteins are GPI anchored proteins localized in Detergent Resistant Microdomains (DRMs) at the plasma membrane and in intracellular compartments such as late endosomes. The mechanisms involved in the intercellular transfer of PrPsc are still enigmatic. Recently, small cellular vesicles of endosomal origin called exosomes have been proposed to contribute to the spread of prions in cell culture models. Retroviruses such as Murine Leukemia Virus (MuLV) or Human Immunodeficiency Virus type 1 (HIV-1) have been shown to assemble and bud into DRMs at the plasma membrane and into intracellular compartments such as late endosomes/multivesicular bodies. Data indicated that host proteins from these compartments can be recruited into nascent viral particles where they retain their biological function and are able to influence virus replication and cell physiology. These data suggest that prion proteins could be recruited by the viral particles during their formation. Here we present data indicating that prion proteins cofractionate with MuLV Gag and Env proteins in DRMs and in late endosomes. Furthermore we report that MuLV infection strongly enhances the release of PrPc, PrPsc and Scrapie infectivity in the supernatant of coinfected cells. Under these conditions we found by Immunogold Electronic Microscopy and immunoprecipitation experiments that PrPc, PrPsc and Scrapie infectivity are recruited by both MuLV virions and exosomes. We propose that retroviruses can be important cofactors involved in the spread of the pathological prion agent. This work is supported by the GIS-PRION 2003&2004, CNRS and INSERM.
IN In Zellkulturen verstärkten Leblanc et al. durch Coinfektionen mit einem Mausleukemievirus die an Virionen und Exosomen gebundene Freisetzung von PrPc, PrPsc und Scrapie-Infektivität ins Medium.
AD P. Leblanc, S. Alais, J.L. Darlix: 1 LaboRetro unité de virologie humaine INSERM U758, Ecole Normale Supérieure de Lyon, 69364 Lyon Cedex 07 (France), IFR 128 Biosciences, Lyon-Gerland, France; I. Porto-Carreiro, G. Raposo: Institut Curie, CNRS-UMR144 Structure et Compartiments Membranaires, 26 rue d'Ulm, 75248 Paris cedex 05, France; S. Lehmann: Institut de Génétique Humaine (IGH), CNRS, UPR 1142, 141 rue de la Cardonille, 34396 Montpellier, Cedex 5, France; J. Grassi: CEA, Service de pharmacologie et d'immunologie, CEA/Saclay, 91191 Gif sur Yvette, France. E-mail: Pascal.Leblanc@ens-lyon.fr
SP englisch
PO Italien