In this work, we have examined the mechanism of action of Pateamine A (Pat A) on the translation of Sindbis virus (SINV) genomic and subgenomic mRNAs.

Pat A is a natural compound obtained from a marine sponge that selectively blocks the initiation factor of translation eIF4A.

We have found that Pat A inhibits the translation of SINV genomic mRNA leading to the arrest of the synthesis of viral non-structural proteins.

Notably, this compound has little effect on protein synthesis directed by subgenomic mRNA in SINV infected cells.

Curiously, inhibition of this mRNA by Pat A is observed in transfected cells and in cell free systems.

This dual mechanism of translation of subgenomic mRNA indicates that eIF4A is not required for its translation in infected cells, but this factor is necessary outside the infection context.

By using Pat A, we have determined the time during infection when there is the switch for eIF4A independent translation of viral subgenomic mRNA.

These findings are of interest to understand the regulation of viral mRNA translation in infected cells.