title: Differential inhibition of cellular and Sindbis virus translation by brefeldin A.
abstract: Brefeldin A is a macrolide compound that interferes with the secretory pathway and also affects protein synthesis in mammalian cells. As a result, this antibiotic impedes the maturation of viral glycoproteins of enveloped viruses and viral genome replication in several virus species. In the present work, we show that translation of subgenomic mRNA from Sindbis virus, which in contrast to cellular translation is resistant to brefeldin A after prolonged treatment. The phosphorylation of eIF2alpha as a result of brefeldin A treatment correlates with the inhibition of cellular translation, while late viral protein synthesis is resistant to this phosphorylation. The effect of brefeldin A on Sindbis virus replication was also examined using a Sindbis virus replicon. Although brefeldin A delayed viral RNA synthesis, translation by non-replicative viral RNAs was not affected, reinforcing the idea that brefeldin A delays viral RNA replication, but does not directly affect Sindbis virus protein synthesis.
authors.affiliation: Centro de Biología Molecular CSIC-UAM, Facultad de Ciencias, Universidad Autónoma, Cantoblanco, 28049 Madrid, Spain. smolina@cbm.uam.es <smolina@cbm.uam.es>
authors.forename: Susana
authors.initials: S
authors.lastname: Molina
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sanz
authors.forename: Vanesa
authors.initials: V
authors.lastname: Madan
authors.forename: Iván
authors.initials: I
authors.lastname: Ventoso
authors.forename: Alfredo
authors.initials: A
authors.lastname: Castelló
authors.forename: Luis
authors.initials: L
authors.lastname: Carrasco
mesh_terms: D018354:Alphavirus Infections / Q000821:virology*; D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology*; D002460:Cell Line / Q000378:metabolism / Q000821:virology; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D012093:Replicon; D012845:Sindbis Virus / Q000187:drug effects / Q000502:physiology*; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects
chemical_list: D015852:Eukaryotic Initiation Factor-2; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D012367:RNA, Viral; D014764:Viral Proteins; D020126:Brefeldin A