Apart from generation of active viral proteins that participate in capsid morphogenesis and genome replication, viral proteases may also target a number of cellular proteins. Proteolysis of these cellular substrates can very much affect a variety of cellular processes and play an important role in virus-induced cytopathogenesis [8, 9] . In this regard, productive poliovirus infection induces rapid morphological alterations in host-cell. Among them, the most prevalent is the accumulation of numerous membranous vesicles in the cytoplasm, derived from endoplasmic reticulum where the viral proteins 2C and 2BC play a central role [10] . In addition, cellular shape is modified upon viral replication giving rise to cell rounding, which is most probably induced by disorders in the cytoskeletal network [11] . Finally, chromatin condensates at late times postinfection, associated with the nuclear envelope except for sites where nuclear pores are placed [11] . Interestingly, individual expression of the viral proteases 2A pro and 3C pro leads to the induction of most of these cytopathic effects, supporting the idea that these proteases actively contribute to the viral-induced morphological changes [12] . Indeed, long-term expression of either 2A pro or 3C pro triggers the activation of caspases and, thus, cell death by apoptosis [11, 12] , reflecting the strong cytotoxicity of both proteases. In addition to the cytopathic effects induced by 2A pro and 3C pro , hydrolysis of host proteins may impact on other cellular functions such as the antiviral responses to virus infection. Activation of innate immunity pathways, as well as the establishment of an antiviral response, is absolutely dependent on signals traversing the nuclear membrane through the nuclear pore complex. Therefore, many viruses block cellular gene expression at different levels, that is, translation, transcription or protein and RNA trafficking between nucleus and cytoplasm. The blockade of active trafficking can inhibit the nuclear import of antiviral signals or prevent the export of cellular mRNAs detrimental to virus processes. All these effects can be achieved by hydrolysis of specific cellular proteins. The precise number of cellular proteins degraded by a viral protease, which is known as the "degradome," still remains unknown for a given viral protease. Perhaps, one of the beststudied proteases in this respect is PV 2A pro . The discovery that PV 2A pro bisects the initiation factor of translation eIF4G leading to the regulation of translation in the infected cells has attracted much attention from many laboratories during the past three decades [13, 14] . More recently, 2A pro has been involved in the alteration of RNA and protein trafficking between the nucleus and the cytoplasm upon proteolysis of several nucleoporins [15] [16] [17] . The present paper focuses on the multifaceted activities of 2A pro and its regulation of different viral and cellular processes.