Figure 1.

Viral strategies to disrupt nucleocytoplasmic trafficking of proteins. Nuclear import pathways mediated by Kapα/Kapβ1 or Kapβ2 are shown. Kapα and Kapβ2 bind proteins or cargos with specific NLSs. Kapβ1 and β2 translocate the import complexes through the NPC via interactions with Nups. The import complexes are dissociated by RanGTP at the nucleoplasmic side of the NPC. Viral proteins (blue starbursts) interact with the depicted host factors to disrupt nuclear transport pathways. 2A^pro and 3C^pro of HRV and PV degrade Nups and block nuclear import of proteins via the Kapα/β1 and Kapβ2 pathways. SARS‐CoV ORF6 protein effectively disrupts nuclear import of phosphorylated STAT1 by tethering PY‐STAT1–Kapα/Kapβ complex to ER/Golgi membranes. Alternatively, EBOV‐VP24 binds Kapα preventing its interaction with phosphorylated STAT1 and hnRNP C1/C2, which accumulate in the cytoplasm. In HPV, while HPV11 L1 binds Kapβ2/β3 and disrupts cargo import, the viral HPV16 L2 protein gets imported into nucleus by binding to Kapβ2, Kapβ3 and Kapα/Kapβ1 complex. To inhibit protein import, L protein of EMCV hyperphosphorylates Nups and binds Ran. ICP27 protein of HSV interacts with Nup62 and blocks nuclear import of proteins via Kapα/Kapβ1 and Kapβ2 pathways. Disruption of nuclear import of proteins by other viruses is discussed in the text.