title: Dual mechanisms of translation initiation of the full-length HIV-1 mRNA contribute to gag synthesis.
abstract: The precursor group-specific antigen (pr55(Gag)) is central to HIV-1 assembly. Its expression alone is sufficient to assemble into virus-like particles. It also selects the genomic RNA for encapsidation and is involved in several important virus-host interactions for viral assembly and restriction, making its synthesis essential for aspects of viral replication. Here, we show that the initiation of translation of the HIV-1 genomic RNA is mediated through both a cap-dependent and an internal ribosome entry site (IRES)-mediated mechanisms. In support of this notion, pr55(Gag) synthesis was maintained at 70% when cap-dependent translation initiation was blocked by the expression of eIF4G- and PABP targeting viral proteases in two in vitro systems and in HIV-1-expressing cells directly infected with poliovirus. While our data reveal that IRES-dependent translation of the viral genomic RNA ensures pr55(Gag) expression, the synthesis of other HIV-1 proteins, including that of pr160(Gag/Pol), Vpr and Tat is suppressed early during progressive poliovirus infection. The data presented herein implies that the unspliced HIV-1 genomic RNA utilizes both cap-dependent and IRES-dependent translation initiation to supply pr55(Gag) for virus assembly and production.
authors.affiliation: HIV-1 Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montréal, Québec, Canada.
authors.forename: Anne
authors.initials: A
authors.lastname: Monette
authors.forename: Fernando
authors.initials: F
authors.lastname: Valiente-Echeverría
authors.forename: Matias
authors.initials: M
authors.lastname: Rivero
authors.forename: Éric A
authors.initials: ÉA
authors.lastname: Cohen
authors.forename: Marcelo
authors.initials: M
authors.lastname: Lopez-Lastra
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mouland
mesh_terms: D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D023061:Gene Order; D005822:Genetic Vectors / Q000235:genetics; D016679:Genome, Viral; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D010442:Peptide Chain Initiation, Translational; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000096:biosynthesis*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D012367:RNA, Viral; D038621:Regulatory Sequences, Ribonucleic Acid; D054301:gag Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1