Studies have demonstrated that C proteins of flavivirus were observed in both
AZD 1480 and nucleus [4], [5], [6] and [7]. However, the exact mechanism by which arthropod-borne flavivirus C protein enters the nucleus is unknown. Nuclear translocation of several proteins containing NLS motif is generally mediated by importins [11]. Since our study confirmed the presence of functional NLS motif on WNV/DENV C protein (Fig. 2A and Supplementary Fig. S2), we investigated the role of importins in mediating the active transportation of flavivirus C protein into nucleus. Co-immunoprecipitation and M2H analyses confirmed that the nuclear translocation of WNV/DENV C protein occurs through importin-dependant pathway (Fig. 1). Using a combination of M2H analysis and Far Western blotting, we showed that C protein associated with importin-α directly and importin-α acted as an adaptor to bind with importin-β. This is the first study that unveils the role of importins in mediating the
active transport of arthropod-borne flaviviruses C protein into nucleus.
