title: RACK1 controls IRES-mediated translation of viruses.
abstract: Fighting viral infections is hampered by the scarcity of viral targets and their variability, resulting in development of resistance. Viruses depend on cellular molecules-which are attractive alternative targets-for their life cycle, provided that they are dispensable for normal cell functions. Using the model organism Drosophila melanogaster, we identify the ribosomal protein RACK1 as a cellular factor required for infection by internal ribosome entry site (IRES)-containing viruses. We further show that RACK1 is an essential determinant for hepatitis C virus translation and infection, indicating that its function is conserved for distantly related human and fly viruses. Inhibition of RACK1 does not affect Drosophila or human cell viability and proliferation, and RACK1-silenced adult flies are viable, indicating that this protein is not essential for general translation. Our findings demonstrate a specific function for RACK1 in selective mRNA translation and uncover a target for the development of broad antiviral intervention.
authors.affiliation: CNRS UPR9022, Institut de Biologie Moléculaire et Cellulaire, 67000 Strasbourg, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Majzoub
authors.affiliation: Université de Strasbourg, 67000 Strasbourg, France; Inserm UMR1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 67000 Strasbourg, France.
authors.forename: Mohamed Lamine
authors.initials: ML
authors.lastname: Hafirassou
authors.affiliation: CNRS UPR9022, Institut de Biologie Moléculaire et Cellulaire, 67000 Strasbourg, France; Université de Strasbourg, 67000 Strasbourg, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Meignin
authors.affiliation: CNRS UPR9022, Institut de Biologie Moléculaire et Cellulaire, 67000 Strasbourg, France.
authors.forename: Akira
authors.initials: A
authors.lastname: Goto
authors.affiliation: CNRS UPR9002, Institut de Biologie Moléculaire et Cellulaire, 67000 Strasbourg, France.
authors.forename: Stefano
authors.initials: S
authors.lastname: Marzi
authors.affiliation: Université de Strasbourg, 67000 Strasbourg, France; Inserm UMR1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 67000 Strasbourg, France.
authors.forename: Antonina
authors.initials: A
authors.lastname: Fedorova
authors.affiliation: USR3149, ESPCI ParisTech, 75005 Paris, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Verdier
authors.affiliation: USR3149, ESPCI ParisTech, 75005 Paris, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Vinh
authors.affiliation: CNRS UPR9022, Institut de Biologie Moléculaire et Cellulaire, 67000 Strasbourg, France; Université de Strasbourg, 67000 Strasbourg, France; Institut d'Etudes Avancées de l'Université de Strasbourg, 67000 Strasbourg, France.
authors.forename: Jules A
authors.initials: JA
authors.lastname: Hoffmann
authors.affiliation: CNRS UPR9002, Institut de Biologie Moléculaire et Cellulaire, 67000 Strasbourg, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Martin
authors.affiliation: Université de Strasbourg, 67000 Strasbourg, France; Inserm UMR1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 67000 Strasbourg, France; Institut Hospitalo-Universitaire (IHU), Pôle hépato-digestif, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Baumert
authors.affiliation: Université de Strasbourg, 67000 Strasbourg, France; Inserm UMR1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 67000 Strasbourg, France. Electronic address: catherine.schuster@unistra.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Schuster
authors.affiliation: CNRS UPR9022, Institut de Biologie Moléculaire et Cellulaire, 67000 Strasbourg, France; Université de Strasbourg, 67000 Strasbourg, France. Electronic address: jl.imler@unistra.fr.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Imler
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D056629:Dicistroviridae / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism / Q000821:virology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016174:Hepacivirus / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology*; D006801:Humans; D007304:Insect Viruses / Q000378:metabolism*; D008958:Models, Molecular; D009363:Neoplasm Proteins / Q000378:metabolism*; D010448:Peptide Initiation Factors / Q000378:metabolism; D014176:Protein Biosynthesis; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D038621:Regulatory Sequences, Ribonucleic Acid; D014779:Virus Replication
chemical_list: D029721:Drosophila Proteins; D009363:Neoplasm Proteins; D010448:Peptide Initiation Factors; C524464:RACK1 protein, Drosophila; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D038621:Regulatory Sequences, Ribonucleic Acid; D019204:GTP-Binding Proteins