Foot-and-mouth disease virus 3C protease induces cleavage of translation initiation factors eIF4A and eIF4G within infected cells

Infection of cells by foot-and-mouth disease virus (FMDV) results in the ra pid inhibition of host cell protein synthesis. This process is accompanied by the early cleavage of the translation initiation factor eIF4G, a compone nt of the cap-binding complex eIF4F, This cleavage is mediated by the leade r (L) protease. Subsequently, as the virus proteins accumulate, secondary c leavages of eIF4G occur. Furthermore, eIF4A (46 kDa), a second component of eIF4F, is also cleaved in these later stages of the infection cycle. The 3 3-kDa cleavage product of eIF4A has lost a fragment from its N terminus. Tr ansient-expression assays demonstrated that eIF4A was not cleaved in the pr esence of FMDV L or with the poliovirus 2A protease (which also mediates eI F4G cleavage) but was cleaved when the FMDV 3C protease was expressed, The FMDV 3C protease was also shown in such assays to induce cleavage of eIF4G, resulting in the production of cleavage products different from those gene rated by the L protease. Consistent with these results, within cells infect ed vith a mutant: FMDV lacking the L protease or within cells containing an FMDV replicon lacking L-P1 coding sequences it was again shown that eIF4A and eIF4G were cleaved.