Infection with EMCV and poliovirus causes dephosphorylation of the translational repressor 4E-BP1, which inhibits cap-dependent translation and contributes to host protein synthesis shutoff.
EMCV and poliovirus infection leads to the dephosphorylation of 4E-BP1, inhibiting cap-dependent translation, which may be the primary cause of host protein synthesis shutoff in EMCV-infected cells.
Infection of cells with picornaviruses, such as poliovirus and encephalomyocarditis virus (EMCV), causes a shutoff of host protein synthesis. The molecular mechanism of the shutoff has been partly elucidated for poliovirus but not for EMCV. Translation initiation in eukaryotes is facilitated by the mRNA 5' cap structure to which the multisubunit translation initiation factor eIF4F binds to promote ribosome binding. Picornaviruses use a mechanism for the translation of their RNA that is independent of the cap structure. Poliovirus infection engenders the cleavage of the eIF4G (formerly p220) component of eIF4F and renders this complex inactive for cap-dependent translation. In contrast, EMCV infection does not result in eIF4G cleavage. Here, we report that both EMCV and poliovirus activate a translational repressor, 4E-BP1, that inhibits cap-dependent translation by binding to the cap-binding subunit eIF4E. Binding of eIF4E occurs only to the underphosphorylated form of 4E-BP1, and this interaction is highly regulated in cells. We show that 4E-BP1 becomes dephosphorylated upon infection with both EMCV and poliovirus. Dephosphorylation of 4E-BP1 temporally coincides with the shutoff of protein synthesis by EMCV but lags behind the shutoff and eIF4G cleavage in poliovirus-infected cells. Dephosphorylation of 4E-BP1 by specifically inhibiting cap-dependent translation may be the major cause of the shutoff phenomenon in EMCV-infected cells.
Gingras et al. (Tue,) conducted a other in Picornavirus infection (EMCV and poliovirus). Infection with encephalomyocarditis virus (EMCV) and poliovirus was evaluated on Dephosphorylation of 4E-BP1 and shutoff of host protein synthesis. Infection with EMCV and poliovirus causes dephosphorylation of the translational repressor 4E-BP1, which inhibits cap-dependent translation and contributes to host protein synthesis shutoff.