title: In vitro studies reveal that different modes of initiation on HIV-1 mRNA have different levels of requirement for eukaryotic initiation factor 4F.
abstract: Expression of the two isoforms p55 and p40 of HIV-1 Gag proteins relies on distinct translation initiation mechanisms, a cap-dependent initiation and two internal ribosome entry sites (IRESs). The regulation of these processes is complex and remains poorly understood. This study was focused on the influence of the 5'-UTR and on the requirement for the eukaryotic initiation factor (eIF)4F complex components. By using an in vitro system, we showed substantial involvement of the 5'-UTR in the control of p55 expression. This highly structured 5'-UTR requires the eIF4F complex, especially RNA helicase eIF4A, which mediates initiation at the authentic AUG codon. In addition, the 5'-UTR regulates expression in an RNA concentration-dependent manner, with a high concentration of RNA triggering specific reduction of full-length Gag p55 production. HIV-1 genomic RNA also has the ability to use a strong IRES element located in the gag coding region. We show that this mechanism is particularly efficient, and that activity of this IRES is only poorly dependent on RNA helicase eIF4A when the viral 5'-UTR is removed. HIV-1 genomic mRNA exhibits in vitro translational features that allow the expression of Gag p55 protein by different mechanisms that involve different requirements for eIF4E, eIF4G, and eIF4A. This suggests that HIV-1 could adapt to its mode of translation according to the availability of the initiation factors in the infected cell.
authors: INSERM U758, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France. sylvain.de.breyne@ens-lyon.fr
authors: Sylvain
authors: S
authors: de Breyne
authors: Nathalie
authors: N
authors: Chamond
authors: Didier
authors: D
authors: Décimo
authors: Mary-Anne
authors: MA
authors: Trabaud
authors: Patrice
authors: P
authors: André
authors: Bruno
authors: B
authors: Sargueil
authors: Théophile
authors: T
authors: Ohlmann
mesh_terms: D020121:5' Untranslated Regions; D003062:Codon; D039562:Eukaryotic Initiation Factor-4F / Q000378:metabolism*; D005814:Genes, Viral; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D003062:Codon; D039562:Eukaryotic Initiation Factor-4F; D012333:RNA, Messenger