Retrovirus infection strongly enhances scrapie infectivity release in cell culture.
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.
Leblanc
Pascal
P
LaboRétro unité de virologie humaine INSERM U758, Ecole Normale Supérieure de Lyon, Lyon Cedex, France. Pascal.Leblanc@ens-lyon.fr
Alais
Sandrine
S
Porto-Carreiro
Isabel
I
Lehmann
Sylvain
S
Grassi
Jacques
J
Raposo
Graça
G
Darlix
Jean Luc
JL
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
D000906:Antibodies; D015683:Gene Products, gag; D018621:PrPC Proteins; D018620:PrPSc Proteins; D014759:Viral Envelope Proteins