The influenza C virus (ICV) is a human pathogenic agent and the infections are frequently identified in children. Compared to influenza A and B viruses， the nucleoprotein of ICV (NPC) has an extended C-terminal region of which the functional significance is ill-defined. We observed that the nuclear localization signals (NLSs) found on the nucleoproteins of influenza A and B subtypes are absent at corresponding positions on ICV. Instead， we found that a long bipartite nuclear localization signal resides at the extended C-terminal region， spanning from R513 to K549. Our experimental data determined that the KKMK motif within this region plays important roles on both nuclear import and polymerase activity. S... More
The influenza C virus (ICV) is a human pathogenic agent and the infections are frequently identified in children. Compared to influenza A and B viruses， the nucleoprotein of ICV (NPC) has an extended C-terminal region of which the functional significance is ill-defined. We observed that the nuclear localization signals (NLSs) found on the nucleoproteins of influenza A and B subtypes are absent at corresponding positions on ICV. Instead， we found that a long bipartite nuclear localization signal resides at the extended C-terminal region， spanning from R513 to K549. Our experimental data determined that the KKMK motif within this region plays important roles on both nuclear import and polymerase activity. Similar to the influenza A viruses， NPC also binds to multiple human importin α isoforms. Taken together， our results enhance the understanding on the virus-host interaction of the influenza C virus. As a member of the Orthomyxoviridae family， the polymerase complex of influenza C structurally resembles its influenza A and influenza B counterparts but the nucleoprotein differs by possessing an extra C-terminal region. We have characterized this region in view of nuclear import and interaction with importin α protein family. Our results demonstrate functional significance of a previously uncharacterized region on Orthomyxoviridae NP. Based on this work， we propose that importin α binding to influenza C NP is regulated by a long bipartite nuclear localization signal. Since the sequence of influenza D NP shares high homology to influenza C， this work will also shed light on how influenza D NP functions.
