The nuclear import receptor importin-7 targets HPV from the Golgi to the nucleus to promote infection.

During human papillomavirus (HPV) entry, the virus exploits COPI-dependent retrograde transport to cross the Golgi apparatus before reaching the nucleus to cause infection. How HPV enters the nucleus after exiting the Golgi is unclear, although mitotic nuclear envelope breakdown (NEB) appears important. Here, we show that importin-7 (IPO7), a nuclear pore import receptor, is present at the Golgi and promotes HPV infection. IPO7 knockdown inhibits infection and causes HPV to accumulate in the Golgi without reaching mitotic chromosomes, demonstrating that IPO7 promotes Golgi-to-nucleus transport of HPV. Golgi-to-nucleus transport of a cellular cargo also requires IPO7, suggesting that HPV hijacks a preexisting pathway for nuclear entry. Furthermore, the C-terminal nuclear localization sequence of HPV L2 protein, which overlaps its cell-penetrating peptide sequence, binds IPO7 directly in a COPI-dependent virus trafficking step. Together, these data identify a role for an importin in HPV infection and suggest that the canonical nuclear pore import machinery plays an unanticipated role in NEB-dependent nuclear entry.