title: Retrovirus infection strongly enhances scrapie infectivity release in cell culture.
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.
authors.affiliation: LaboRétro unité de virologie humaine INSERM U758, Ecole Normale Supérieure de Lyon, Lyon Cedex, France. Pascal.Leblanc@ens-lyon.fr
authors.forename: Pascal
authors.initials: P
authors.lastname: Leblanc
authors.forename: Sandrine
authors.initials: S
authors.lastname: Alais
authors.forename: Isabel
authors.initials: I
authors.lastname: Porto-Carreiro
authors.forename: Sylvain
authors.initials: S
authors.lastname: Lehmann
authors.forename: Jacques
authors.initials: J
authors.lastname: Grassi
authors.forename: Graça
authors.initials: G
authors.lastname: Raposo
authors.forename: Jean Luc
authors.initials: JL
authors.lastname: Darlix
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D018929:Cell Culture Techniques; D015683:Gene Products, gag / Q000378:metabolism; D006801:Humans; D051379:Mice; D008979:Moloney murine leukemia virus / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D041681:NIH 3T3 Cells; D018621:PrPC Proteins / Q000378:metabolism / Q000648:ultrastructure; D018620:PrPSc Proteins / Q000378:metabolism / Q000648:ultrastructure; D012192:Retroviridae Infections / Q000150:complications* / Q000821:virology; D012608:Scrapie / Q000150:complications* / Q000473:pathology*; D014759:Viral Envelope Proteins / Q000276:immunology; D014771:Virion / Q000378:metabolism
chemical_list: D000906:Antibodies; D015683:Gene Products, gag; D018621:PrPC Proteins; D018620:PrPSc Proteins; D014759:Viral Envelope Proteins