Infection of animal cells with FMDV also leads to proteolysis of eIF4G and to rapid inhibition of cellular translation [48] . The proteolysis of eIF4G is carried out by the two virally encoded proteases L pro and 3C pro [144, 145] . L pro cleaves both eIF4GI and eIF4GII extremely rapidly at positions 674 ( Figure 3) and 700, respectively, located seven and one amino acids upstream of the 2A pro cleavage sites on eIF4GI and eIF4GII [50, 146] . The cleavage of eIF4G by FMDV L pro results in the rapid shutoff of host-cell protein synthesis [145] . Although the initial cleavage of eIF4GI can be carried out by FMDV L pro in the absence of virus replication [145] , a sequential cleavage of the C-terminal fragment of eIF4GI by FMDV 3C pro also occurs in BHK cells at early stages of infection concomitant with the shutdown of viral translation. The 3C pro cleavage site on eIF4GI has been located at position 712, 38 amino acids downstream of the L pro cleavage site [147] although the role of this sequential cleavage is still unclear. The amino acid segment of eIF4G located between the L pro and 3C pro cleavage sites binds RNA and was suggested to be critical for mRNA scanning by the preinitiation complex [148] . Interestingly, this secondary cleavage does not occur in human cell lines due to an amino acid substitution at the cleavage site on eIF4GI [147] .