title: Translational regulation of APOBEC3G mRNA by Vif requires its 5'UTR and contributes to restoring HIV-1 infectivity.
abstract: The essential HIV-1 viral infectivity factor (Vif) allows productive infection of non-permissive cells expressing cytidine deaminases APOBEC3G (A3G) and A3F by decreasing their cellular level, and preventing their incorporation into virions. Unlike the Vif-induced degradation of A3G, the functional role of the inhibition of A3G translation by Vif remained unclear. Here, we show that two stem-loop structures within the 5'-untranslated region of A3G mRNA are crucial for translation inhibition by Vif in cells, and most Vif alleles neutralize A3G translation efficiently. Interestingly, K26R mutation in Vif abolishes degradation of A3G by the proteasome but has no effect at the translational level, indicating these two pathways are independent. These two mechanisms, proteasomal degradation and translational inhibition, similarly contribute to decrease the cellular level of A3G by Vif and to prevent its incorporation into virions. Importantly, inhibition of A3G translation is sufficient to partially restore viral infectivity in the absence of proteosomal degradation. These findings demonstrate that HIV-1 has evolved redundant mechanisms to specifically inhibit the potent antiviral activity of A3G.
authors.affiliation: Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR 9002, IBMC-15 rue René Descartes, F-67000, Strasbourg, France.
authors.forename: Santiago
authors.initials: S
authors.lastname: Guerrero
authors.affiliation: Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR 9002, IBMC-15 rue René Descartes, F-67000, Strasbourg, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Libre
authors.affiliation: Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR 9002, IBMC-15 rue René Descartes, F-67000, Strasbourg, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Batisse
authors.affiliation: Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR 9002, IBMC-15 rue René Descartes, F-67000, Strasbourg, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Mercenne
authors.affiliation: Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR 9002, IBMC-15 rue René Descartes, F-67000, Strasbourg, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Richer
authors.affiliation: Université de Strasbourg, INSERM, UMR 1109, Laboratoire d'ImmunoRhumatologie Moléculaire, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Institut de Virologie, 3 rue Koeberlé, F-67000 Strasbourg, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Laumond
authors.affiliation: Université de Strasbourg, INSERM, UMR 1109, Laboratoire d'ImmunoRhumatologie Moléculaire, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Institut de Virologie, 3 rue Koeberlé, F-67000 Strasbourg, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Decoville
authors.affiliation: Université de Strasbourg, INSERM, UMR 1109, Laboratoire d'ImmunoRhumatologie Moléculaire, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Institut de Virologie, 3 rue Koeberlé, F-67000 Strasbourg, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Moog
authors.affiliation: Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR 9002, IBMC-15 rue René Descartes, F-67000, Strasbourg, France.
authors.forename: Roland
authors.initials: R
authors.lastname: Marquet
authors.affiliation: Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR 9002, IBMC-15 rue René Descartes, F-67000, Strasbourg, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Paillart
mesh_terms: D020121:5' Untranslated Regions; D000071480:APOBEC-3G Deaminase / Q000235:genetics* / Q000378:metabolism*; D000483:Alleles; D000998:Antiviral Agents / Q000494:pharmacology; D043525:Cytosine Deaminase / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D057809:HEK293 Cells; D015658:HIV Infections / Q000235:genetics*; D006801:Humans; D009154:Mutation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D020121:5' Untranslated Regions; D000998:Antiviral Agents; D012333:RNA, Messenger; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; D046988:Proteasome Endopeptidase Complex; C492906:APOBEC3F protein, human; D043525:Cytosine Deaminase; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human