Article
- The EMBO Journal (2006) 25, 2674 - 2685
- doi:10.1038/sj.emboj.7601162
Published online: 25 May 2006
Subject Categories:
Retrovirus infection strongly enhances scrapie infectivity release in cell culture
Pascal Leblanc1,2, Sandrine Alais1,2, Isabel Porto-Carreiro3, Sylvain Lehmann4, Jacques Grassi5, Graça Raposo3 and Jean Luc Darlix1,2
- LaboRétro unité de virologie humaine INSERM U758, Ecole Normale Supérieure de Lyon, Lyon Cedex, France
- IFR 128 Biosciences Lyon-Gerland, France
- Institut Curie, CNRS-UMR144 Structure et Compartiments Membranaires, Paris Cedex, France
- Institut de Génétique Humaine (IGH), CNRS, UPR 1142, Montpellier Cedex, France
- CEA, Service de pharmacologie et d'immunologie, CEA/Saclay, Gif sur Yvette, France
Correspondence to:
Pascal Leblanc, LaboRétro unité de virologie humaine, INSERM U758, Ecole Normale Supérieure de Lyon, 46 allée d'ltalie, 69364 Lyon Cedex 07, France. Tel.: +33 472728625; Fax: +33 472728080; E-mail: Pascal.Leblanc@ens-lyon.fr
Received 4 January 2006; Accepted 2 May 2006
Abstract
Prion diseases are neurodegenerative disorders associated in most cases with the accumulation in the central nervous system of PrPSc (conformationally altered isoform of cellular prion protein (PrPC); Sc for scrapie), a partially protease-resistant isoform of the PrPC. PrPSc is thought to be the causative agent of transmissible spongiform encephalopathies. 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 detergent-resistant microdomains and into intracellular compartments such as late endosomes/multivesicular bodies. Here we report that moloney murine leukemia virus (MoMuLV) infection strongly enhances the release of scrapie infectivity in the supernatant of coinfected cells. Under these conditions, we found 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.
Keywords:
- exosome,
- infectivity,
- MoMuLV,
- PrP,
- retroviruses
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