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Conventional nuclear import is independent of the cytoskeleton, but recent data have shown that the import of specific proteins can be either facilitated or inhibited by microtubules (MTs). Nuclear import of the P-protein from rabies virus involves a MT-facilitated mechanism, but here, we show that P-protein is unique in that it also undergoes MT-inhibited import, with the mode of MT-interaction being regulated by the oligomeric state of the P-protein. This is the first demonstration that a protein can utilise both MT-inhibited and MT-facilitated import mechanisms, and can switch between these different modes of MT interaction to regulate its nuclear trafficking. Importantly, we show that the P-protein exploits MT-dependent mechanisms to manipulate host cell processes by switching the import of the interferon-activated transcription factor STAT1 from a conventional to a MT-inhibited mechanism. This prevents STAT1 nuclear import and signalling in response to interferon, which is vital to the host innate antiviral response. This is the first report of MT involvement in the viral subversion of interferon signalling that is central to virus pathogenicity, and identifies novel targets for the development of antiviral drugs or attenuated viruses for vaccine applications.


  • Supplementary material available online at

  • This research was supported by the National Health and Medical Research Council, Australia (Project grant 384107, fellowship 384109). The authors acknowledge Ariad Pharmaceuticals (Cambridge, MA) for supplying the Ariad Inducible Homodimerisation Kit, Yi-Ling Lin for supplying the STAT1-dsRed2 vector, Roger Tsien for supplying the α-tubulin-mCherry vector and Minoru Yoshida for the gift of LMB. G.W.M. also acknowledges the staff of Monash Micro Imaging facility for their help and advice, and Cassandra David for support with cell culture.

  • Accepted July 20, 2009.
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