An alternative hypothesis has been proposed as the cause of the redistribution of nuclear factors. Belov and colleagues reported that the nuclear envelope is permeabilized on PV infection, allowing nuclear proteins to diffuse across the nuclear membrane [196] . Indeed, electron microscopy revealed that PV 2A pro induces severe structural damage in NPC [196] . However, this hypothesis did not clarify why other proteins resident in the nucleus do not diffuse to the cytoplasm after PV infection. Both protein nuclear import and permeabilization of nuclear envelope could be integrated together as sequential steps in PV biological cycle. Protein import blockade is detected early after infection [16] , correlating with the first modifications in the NPC (see below). However, prolonged expression of viral proteins might induce nuclear membrane leakiness, reflected by stronger alterations in NPC architecture [196] . Nevertheless, what might the biological relevance of these events be for a cytoplasmic virus? The most evident answer, which was extensively commented above, is that inhibition of nuclear protein import and further nuclear envelope leakiness might increase the presence of nuclear proteins in the cytoplasm of infected cells, which has been proposed in some cases to play a relevant role in PV replication. In addition, many transcription factors are arrested in the cytoplasm of uninfected cells (e.g., NF-κB, IRF7, and IRF3), but they are immediately activated and imported to the nucleus after proinflammatory extracellular signals or on the activation of intracellular sensors as a consequence of the viral replication. Once in the nucleus, these factors trigger the transcription of a set of genes involved in the antiviral response [197] . Inhibiting the import of these transcription factors, PV might prevent or, at least attenuate, the establishment of a hostile intracellular environment. Further effort will be made in the future to explore this attractive hypothesis.