Nuclear transport factor IPO4 modifies localization by PCV2 and facilitates viral replication

Nuclear transport receptors (NTRs) serve as critical targets hijacked by viruses to enhance their replication and dissemination. In this study, we confirmed the direct interaction between the capsid protein (Cap) of porcine circovirus type 2 (PCV2) and importin 4 (IPO4), a nuclear transport receptor, through mass spectrometry, co-immunoprecipitation, and glutathione-S-transferase pull-down assays. Fine mapping revealed that the N-terminal amino acid residues 1-100 of Cap constitute the critical domain for efficient binding to IPO4. Further investigation showed that the binding of Cap to IPO4 did not trigger its nuclear import function or affect Cap degradation. Instead, it caused IPO4 to translocate from the cytoplasm to the nucleus. Knockdown of IPO4 significantly reduced intracellular levels of PCV2 Cap and inhibited PCV2 replication, suggesting that IPO4 is functionally involved in facilitating viral replication. Collectively, our findings demonstrate that during PCV2 infection, IPO4 binds with Cap to migrate to the nucleus, facilitating viral replication.