Due to their large genomes, poxviruses encode a number of enzymes, including a DNA polymerase and a DNA-dependent RNA polymerase, and therefore require few host gene factors for their replication. Several studies have shown several host nuclear factors are in fact recruited to viral sites of replication. Using bioinformatics we identified a putative bipartite nuclear localization signal in vaccinia virus N2L. Through immuno-precipitation, we were able to show that N2 interacts with two nuclear import proteins, karyopherins (KPN) alpha 2 and alpha 4. Immunofluorescence analysis indicated that in the presence of N2, KPNα2 was found evenly dispersed throughout the cell. However, when N2 is absent from the infection, KPNα2 accumulates at the nuclear periphery. Using Fluorescence Recovery After Photobleaching (FRAP), we show that the presence of N2 retards the nuclear turnover rate of KPNα2. Taken together, we suggest that N2 is competing for available KPNα2 to modulate nuclear transport thus promoting virulence.