title: Functional mechanisms of the cellular prion protein (PrP(C)) associated anti-HIV-1 properties.
abstract: The cellular prion protein PrP(C)/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 PrP(C) 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 PrP(C) displays important similarities with the HIV-1 nucleocapsid protein and found that PrP(C) expression in a human cell line strongly reduced HIV-1 expression and virus production. Using different PrP(C) 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 PrP(C) 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 PrP(C) colocalizes with the virus assembly machinery at the plasma membrane and at the virological synapse in infected T cells. Depletion of PrP(C) in infected T cells and microglial cells favors HIV-1 replication, confirming its negative impact on the HIV-1 life cycle.
authors.affiliation: Université de Lyon, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Alais
authors.forename: Ricardo
authors.initials: R
authors.lastname: Soto-Rifo
authors.forename: Vincent
authors.initials: V
authors.lastname: Balter
authors.forename: Henri
authors.initials: H
authors.lastname: Gruffat
authors.forename: Evelyne
authors.initials: E
authors.lastname: Manet
authors.forename: Laurent
authors.initials: L
authors.lastname: Schaeffer
authors.forename: Jean Luc
authors.initials: JL
authors.lastname: Darlix
authors.forename: Andrea
authors.initials: A
authors.lastname: Cimarelli
authors.forename: Graça
authors.initials: G
authors.lastname: Raposo
authors.forename: Théophile
authors.initials: T
authors.lastname: Ohlmann
authors.forename: Pascal
authors.initials: P
authors.lastname: Leblanc
mesh_terms: D015703:Antigens, CD / Q000235:genetics; D002460:Cell Line; D002478:Cells, Cultured; D058851:GPI-Linked Proteins / Q000235:genetics; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D015683:Gene Products, gag / Q000032:analysis; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D006801:Humans; D009154:Mutation; D018621:PrPC Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000821:virology*; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D015683:Gene Products, gag; D018621:PrPC Proteins; D012367:RNA, Viral; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2
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