title: Differential action of pateamine A on translation of genomic and subgenomic mRNAs from Sindbis virus.
abstract: Pateamine A (Pat A) is a natural marine product that interacts specifically with the translation initiation factor eIF4A leading to the disruption of the eIF4F complex. In the present study, we have examined the activity of Pat A on the translation of Sindbis virus (SINV) mRNAs. Translation of genomic mRNA is strongly suppressed by Pat A, as shown by the reduction of nsP1 or nsP2 synthesis. Notably, protein synthesis directed by subgenomic mRNA is resistant to Pat A inhibition when the compound is added at late times following infection; however, subgenomic mRNA is sensitive to Pat A in transfected cells or in cell free systems, indicating that this viral mRNA exhibits a dual mechanism of translation. A detailed kinetic analysis of Pat A inhibition in SINV-infected cells demonstrates that a switch occurs approximately 4h after infection, rendering subgenomic mRNA translation more resistant to Pat A inhibition.
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), C/Nicolás Cabrera, 1, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: González-Almela
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), C/Nicolás Cabrera, 1, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Sanz
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), C/Nicolás Cabrera, 1, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: García-Moreno
authors.affiliation: School of Chemical and Physical Sciences, Victoria University of Wellington, Wellington 6140, New Zealand.
authors.forename: Peter
authors.initials: P
authors.lastname: Northcote
authors.affiliation: Department of Biochemistry and Goodman Cancer Center, McIntyre Medical Sciences Building, 3655 Promenade Sir William Osler, McGill University, Montreal, Quebec, Canada H3G 1Y6.
authors.forename: Jerry
authors.initials: J
authors.lastname: Pelletier
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), C/Nicolás Cabrera, 1, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain. Electronic address: lcarrasco@cbm.csic.es.
authors.forename: Luis
authors.initials: L
authors.lastname: Carrasco
mesh_terms: D000818:Animals; D002460:Cell Line; D004852:Epoxy Compounds / Q000378:metabolism*; D039601:Eukaryotic Initiation Factor-4A / Q000037:antagonists & inhibitors; D018942:Macrolides / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D012845:Sindbis Virus / Q000187:drug effects* / Q000502:physiology; D013844:Thiazoles / Q000378:metabolism*; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D004852:Epoxy Compounds; D018942:Macrolides; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D012367:RNA, Viral; D013844:Thiazoles; C421324:pateamine A; D039601:Eukaryotic Initiation Factor-4A
keywords: Alphavirus protein synthesis; Helicase inhibitor; Sindbis virus; Translation inhibitors; eIF4A