Differential action of pateamine A on translation of genomic and subgenomic mRNAs from Sindbis virus

© 2015 Elsevier Inc. 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....

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Detalles Bibliográficos
Autores: González-Almela, Esther, Sanz, Miguel Ángel, García-Moreno, Manuel, Northcote, Peter, Pelletier, Jerry, Carrasco Llamas, Luis
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/133519
Acceso en línea:http://hdl.handle.net/10261/133519
Access Level:acceso abierto
Palabra clave:Alphavirus protein synthesis
eIF4A Sindbis virus
Helicase inhibitor
Translation inhibitors
Descripción
Sumario:© 2015 Elsevier Inc. 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 4. h after infection, rendering subgenomic mRNA translation more resistant to Pat A inhibition.