Caspases are not involved in the cleavage of translation initiation factorelF4GI during picornavirus infection

Infection of cells by many picornaviruses results in the rapid inhibition o f cellular protein synthesis due to cleavage of the translation initiation factor eIF4G. The poliovirus (PV) 2A and foot-and-mouth disease virus (FMDV ) L proteases are each sufficient to mediate this cleavage, but the cleavag e mechanism may be indirect, involving an unidentified cellular protease(s) , eIF4G is also targetted for cleavage by caspase-3 during apoptosis. Here, it is shown that caspase inhibitors do not inhibit the cleavage of eIF4GI during PV or FMDV infection. Similarly, in transient-expression studies, th e cleavage of eIF4GI induced by PV 2A or FMDV L was unaffected by these inh ibitors. Furthermore, the cleavage of eIF4GI was observed in PV-infected MC F-7 cells lacking caspase-3. These data, and the fact that induction of apo ptosis yields different eIF4GI cleavage fragments, indicate that caspases d o not have a major role in the cleavage of eIF4GI during PV or FMDV infecti on.