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Cellular and Molecular Life Sciences 69, 8 (2012) 1331-1352
Functional mechanisms of the cellular prion protein (PrPC) associated anti-HIV-1 properties
Sandrine Alais 1, 2, Ricardo Soto-Rifo 1, 2, Vincent Balter 3, Henri Gruffat 1, 2, Evelyne Manet 1, 2, Laurent Schaeffer 4, Jean-Luc Darlix 1, 2, Andrea Cimarelli 1, 2, Graça Raposo 5, Théophile Ohlmann 1, 2, Pascal Leblanc 1, 4

The cellular prion protein PrPC/CD230 is a GPI-anchor protein highly expressed in cells from the nervous and immune systems and well conserved among vertebrates. In the last decade, several studies suggested that PrPC displays antiviral properties by restricting the replication of different viruses, and in particular retroviruses such as murine leukemia virus (MuLV) and the human immunodeficiency virus type 1 (HIV-1). In this context, we previously showed that PrPC displays important similarities with the HIV-1 nucleocapsid protein and found that PrPC expression in a human cell line strongly reduced HIV-1 expression and virus production. Using different PrPC mutants, we report here that the anti-HIV-1 properties are mostly associated with the amino-terminal 24-KRPKP-28 basic domain. In agreement with its reported RNA chaperone activity, we found that PrPC binds to the viral genomic RNA of HIV-1 and negatively affects its translation. Using a combination of biochemical and cell imaging strategies, we found that PrPC colocalizes with the virus assembly machinery at the plasma membrane and at the virological synapse in infected T cells. Depletion of PrPC in infected T cells and microglial cells favors HIV-1 replication, confirming its negative impact on the HIV-1 life cycle
1 :  Virologie humaine
INSERM : U758 – IFR128 – École Normale Supérieure (ENS) - Lyon
2 :  Université de Lyon
PRES Université de Lyon
3 :  Laboratoire de Géologie de Lyon - Terre, Planètes, Environnement (LGL-TPE)
CNRS : UMR5276 – INSU – Université Claude Bernard - Lyon I (UCBL) – École Normale Supérieure (ENS) - Lyon
4 :  Laboratoire de Biologie Moléculaire de la Cellule (LBMC)
CNRS : UMR5239 – Institut national de la recherche agronomique (INRA) : UR5239 – Université Claude Bernard - Lyon I (UCBL) – École Normale Supérieure (ENS) - Lyon
5 :  Compartimentation et dynamique cellulaires (CDC)
CNRS : UMR144 – Institut Curie – Université Pierre et Marie Curie (UPMC) - Paris VI
Sciences du Vivant/Biochimie, Biologie Moléculaire

Sciences du Vivant/Biologie cellulaire
Prion – PrPC – HIV-1 – Restriction factor – Anti-viral – RNA – Translation