The biological cycle of picornaviruses is confined to the cytoplasm of infected cells. However, some of the PV proteins are able to target nuclear proteins such as transcription and splicing factors and proteins involved in nuclear-cytoplasmic trafficking. One of the best studied cases in this regard is the cleavage of nucleoporins (Nups), components of the nuclear pore complex (NPC), by PV and HRV 2A pro , which directly impacts on nuclear-cytoplasmic trafficking of proteins and RNAs [15, 16, 159] . Complementarily, EMCV L protein affects on the phosphorylation status of Nup62 and induces similar effects to those described for PV 2A pro in the transport of macromolecules through NPC [160] . Nevertheless, Nups are not only targets for picornavirus proteins but also for matrix (M) protein from Vesicular stomatitis virus (VSV) [161] and nonstructural protein 1 (NS1) from influenza virus [162] , which also impair components of the nuclear export-import host machinery following analogous mechanisms. Taking into account that proteins from different positive and negative strand RNA viruses target Nups, we highlight in this paper NPC as a key target for viral proteins, although the possible role of NPC in virus biological cycle is still under intensive research.