Importinα3 Mediates BmNPV Nucleocapsid Nuclear Entry via a Ran-Independent Pathway.

Baculoviruses, such as Bombyx mori nucleopolyhedrovirus (BmNPV), are arthropod-specific DNA viruses with a complex entry mechanism that relies on host importin proteins for nuclear import. Despite significant advances in understanding viral entry, the precise role of importins in BmNPV nuclear import remains poorly understood. In this study, we identify importin α3 (IMPα3) as a critical mediator for the nuclear entry of the BmNPV nucleocapsid. Using RT-qPCR, we found that IMPα3, along with IMPα5 and IMP13, is upregulated during the early stages of BmNPV infection. Knockdown of IMPα3 significantly reduced viral infection rates, while overexpression of IMPα3 increased the infection rate by 24%. Functional domain analysis revealed that the N- and C-terminal regions of IMPα3 are essential for nucleocapsid nuclear entry, with truncation of either domain impairing this process. Interestingly, our findings indicate that BmNPV nuclear entry is independent of the classical RanGTP hydrolysis pathway, suggesting a Ran-independent mechanism for nucleocapsid transport. Further analysis confirmed that IMPα3, but not IMPβ, is essential for nuclear import, bypassing the need for traditional importin β-mediated transport. These results provide new insights into the role of IMPα3 in BmNPV infection and suggest that targeting IMPα3 could be a promising strategy for antiviral intervention.