In agreement with what was observed with the addition of exogenous recombinant proteins [136] , translation of de novo synthesized mRNAs showed higher susceptibility to low doses of PV 2A pro than mRNAs already engaged in translational machinery [95] . These results suggested a possible specific role of eIF4GI in the pioneer round of translation in agreement with a previous report [139] . However, specific ablation of eIF4GI using siRNAs induced a moderate inhibition of luciferase synthesis from de novo synthesized and preexisting mRNA (about 40% in both cases) [96] . These findings reported by Welnowska and colleagues indicated that the higher susceptibility of de novo synthesized mRNA translation to low doses of IRES-2A might be produced by an additional effect of PV 2A pro on another gene expression step. In this regard, further studies demonstrate that the stronger impact of 2A pro on de novo synthesized mRNAs is due to the concomitant inhibition of RNA nuclear export by Nucleoporin 98 cleavage, which is also achieved under these conditions (see below) [17] . Interestingly, cellular mRNAs are able to initiate translation after a polysome runoff with high salt treatment when eIF4GI is totally cleaved by PV 2A pro , whereas it is completely abolished when both forms of eIF4G are proteolyzed [95] . Taken together these set of data from cell expressing 2A pro [95, 136] as well as from PV-infected cells [120] [121] [122] we can conclude that complete shutoff of the protein synthesis induced by PV 2A pro is achieved when both eIF4GI and eIF4GII are completely cleaved. Therefore, when the levels of one of the two populations of eIF4G remain unaffected either because it is not cleaved by PV 2A pro [95] or it is not depleted by siRNAs [96] , extensive host protein synthesis takes place.