PV results in a rapid shutoff of host-cell protein synthesis, whereas viral mRNA translation takes place efficiently [108] . It was initially observed that the inhibition of host-cell translation in PV-infected cells correlated with the proteolysis of a component of the eIF4F complex with a molecular mass of about 220 kDa (later identified as eIF4G) [39, 109] . This cleavage is exerted by 2A pro and can be prevented by both insertion of mutations that abolish the protease activity and addition of 2A inhibitors [76, 110, 111] . Interestingly, this proteolysis is more effective when eIF4E is interacting with eIF4G, suggesting that PV 2A pro preferentially acts on the eIF4G pool involved in translation [112] . Cleavage of eIF4GI also occurs in cells infected with other picornaviruses such as HRV, coxsackievirus, and FMDV [48, 113, 114] . Interestingly, 2A pro from PV, HRV, and coxsackieviruses cleave eIF4GI at positions 681/682 (Figure 3 ), suggesting the conservation of the specificity of enterovirus 2A proteases for the substrate determinants present in eIF4GI [114, 115] . Cleavage at position 681/682 separates eIF4E-and eIF3binding sites of eIF4GI, contained in N-terminal and Cterminal fragments respectively, thus decoupling mRNA and ribosome recruiting activities. The PV 2A pro cleaves eIF4GI directly and does not require any additional proteins for this process to occur [116, 117] . However, the fact that PV 2A pro is not copurified with eIF4GI fragments from PV-infected cell extracts suggest that 2A pro induced the activation of a host protease, which in turn cleaves eIF4G during PV infection [112] . In addition, it has been proposed that eIF3 and an unknown host-cell protein could act as cofactors for eIF4GI cleavage by PV 2A pro [118] . In this sense, Zamora and colleagues suggested that PV infection activates at least two host-cell proteases, which together with PV 2A pro , cleave eIF4GI [119] . Nevertheless, no additional evidence has been put forward to support this hypothesis and the identity of these host proteases has not yet been determined.