PROTEOLYSIS OF HUMAN EUKARYOTIC TRANSLATION INITIATION-FACTOR EIF4GII, BUT NOT EIF4GI, COINCIDES WITH THE SHUTOFF OF HOST PROTEIN-SYNTHESISAFTER POLIOVIRUS INFECTION

Eukaryotic initiation factor (eIF) 4GI is a component of the cap-bindi ng protein complex eIF4F, which is required for cap-dependent translat ion. Infection of cells by poliovirus results in a precipitous decline of host cell protein synthesis, which is preceded by the cleavage of eIF4GI, Cleavage of eIF4GI results in the inhibition of cap-dependent translation. Poliovirus translation is not affected by eIF4GI cleavage , however, because poliovirus mRNA is translated by a cap-independent mechanism. Cleavage of eIF4GI alone cannot explain the shutoff of host protein synthesis, because after infection in the presence of inhibit ors of virus replication, eIF4GI is cleaved, yet host protein synthesi s is only partially inhibited. Here we show that eIF4GII, a recently d iscovered functional homolog of eIF4GI, is more resistant to polioviru s-mediated cleavage than eIF4GI, and that its proteolysis is concomita nt with the shutoff of host cell protein synthesis. Moreover, infectio n with poliovirus in the presence of inhibitors of virus replication r esulted in efficient cleavage of eIF4GI, but only partial proteolysis of eIF4GII. Thus, cleavage of both eIF4GI and eIF4GII appears to be re quired for the shutoff of host protein synthesis after poliovirus infe ction. These results explain several earlier reports documenting the l ack of correlation between eIF4GI cleavage and inhibition of cellular mRNA translation after poliovirus infection.