Interestingly, Nup98, Nup153 and Nup62, components of the NPC belonging to FG Nup family, were found to be degraded in PV-as well as HRV-infected cells (Figure 4 ) [15, 16, 159] . These proteins are essential factors of the nuclear-cytoplasmic trafficking machinery since their Nterminal FG-rich domains serve as docking sites for soluble transport factors [163, 198] . Nup98, Nup153 and Nup62 are proteolyzed in PV-infected cells following different kinetics. Thus, Nup98 is the cleaved early after infection (from 1 hpi), whereas Nup153 and Nup62 are targeted at late times after infection (from 4 hpi) [15, 16] . In agreement with these findings, cleavage of Nup98 is induced even in presence of inhibitors of PV replication, suggesting that small amounts of viral proteins are sufficient for this proteolysis to occur. However, cleavage of Nup153, and Nup62 are efficiently prevented on arrest of viral replication, probably because they are only efficiently achieved when large amounts of viral proteins are produced [16] . Therefore, Nup98, Nup153, and Nup62 exhibit different susceptibilities to PV replication, thus PV might have a gradual impact on the nuclear-cytoplasmic trafficking machinery. Nup153 is also proteolyzed by caspase-3 and caspase-9 during apoptosis induction; however, the involvement of these cellular proteases in PV-induced Nup cleavage has been ruled out by different laboratories. First, Nup153 cleavage Journal of Biomedicine and Biotechnology 13 products generated upon caspase activation differ to those found in PV-infected cells [159] . In addition, Nup62 is cleaved in PV-infected cells, but it remains intact despite caspase activation [199] . Most importantly, PV-induced NPC structural damage takes place in cells lacking caspase 3 and 9 [196] , and Nup153 and Nup62 are efficiently cleaved in PV-infected cells even in presence of the caspase inhibitor Z-VAD [159] . All together, these data support the idea that one or more viral proteins play a direct role in the cleavage of those Nups. In agreement with this hypothesis, PV-induced NPC damage is prevented by PV 2A pro inhibitors such as elastatinal, elastase, and MPCMK, suggesting an involvement of this viral protease in the alteration of NPC [196] . Indeed, individual expression of PV 2A pro in HeLa cells as well as addition of this protease to cell-free systems gives rise to Nup98, Nup62, and Nup153 cleavage [16, 17, 200] .