The nuclear import machinery is a determinant of influenza virus host adaptation.

After viral entry into the cell, the nuclear envelope poses a major cellular barrier that needs to be overcome upon adaptation of highly pathogenic avian influenza viruses (HPAIV) to the new host. To ensure efficient viral transcription and replication in the nucleus of the host cell, the viral polymerase complex of avian influenza viruses needs to switch from recognition of avian to mammalian components of the nuclear import machinery. Recent evidence suggests that influenza viruses have evolved different mechanisms to utilize importin-α isoforms as components of this machinery, bridging pre- and post-nuclear import on both sides of the nuclear envelope.