Enterovirus-Induced miR-141 Contributes to Shutoff of Host Protein Translation by Targeting the Translation Initiation Factor eIF4E

SummaryViruses rely on the host translation machinery to complete their life cycles. Picornaviruses use an internal ribosome entry site to initiate cap-independent protein translation and in parallel host cap-dependent translation is shut off. This process is thought to occur primarily via cleavage of host translation initiation factors eIF4GI and eIF4GII by viral proteases. Here we describe another mechanism whereby miR-141 induced upon enterovirus infection targets the cap-dependent translation initiation factor, eIF4E, for shutoff of host protein synthesis. Knockdown of miR-141 reduces viral propagation, and silencing of eIF4E can completely reverse the inhibitory effect of the miR-141 antagomiR on viral propagation. Ectopic expression of miR-141 promotes the switch from cap-dependent to cap-independent translation. Moreover, we identified a transcription factor, EGR1, which is partly responsible for miR-141 induction in response to enterovirus infection. Our results suggest that upregulation of miR-141 upon enterovirus infection can facilitate viral propagation by expediting the translational switch.

Graphical AbstractFigure optionsDownload high-quality image (272 K)Download as PowerPoint slideHighlights
► Enterovirus infection induced miR-141 expression
► miR-141 suppressed the translation initiation factor eIF4E
► Knockdown of miR-141 reduced viral production
► Silencing eIF4E rescued the inhibitory effect of miR-141 knockdown