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J. Virol., Mar 1997, 1850-1856, Vol 71, No. 3
Copyright © 1997, American Society for Microbiology

The NPI-1/NPI-3 (karyopherin alpha) binding site on the influenza a virus nucleoprotein NP is a nonconventional nuclear localization signal

P Wang, P Palese and RE O'Neill
Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029, USA.

Two cellular proteins, NPI-1 and NPI-3, were previously identified through their interaction with the influenza virus nucleoprotein (NP) by using the yeast two-hybrid system. These proteins were then shown to act as general transport factors (karyopherin alpha) and nuclear pore- docking proteins to facilitate the transport of the NP and of viral RNA into the nucleus. The yeast two-hybrid assay has now been used to identify the specific domains on the NP that bind to the NPI proteins. Mutational analysis including alanine scanning identified the motifs SxGTKRSYxxM and TKRSxxxM, which are required for binding to NPI-1 and NPI-3, respectively. These sequences were shown to possess nuclear localization signal (NLS) activity following expression of fusion proteins in HeLa cells. These sequences represent a novel nonconventional NLS motif. Another NLS activity not mediated by the NPI binding sites is associated with noncontiguous sequences in the NP.

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