Nuclear import of influenza A viral ribonucleoprotein complexes is mediated by two nuclear localization sequences on viral nucleoprotein

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Abstract
The influenza A virus replicates in the nucleus of its host cell. Thus, entry of the influenza genome into the cell nucleus is necessary for establishing infection. The genome of the influenza A virus consists of eight single-stranded, negative-sense RNA molecules, individually packed with several copies of the viral nucleoprotein (NP) into ribonucleoprotein particles (vRNPs). These vRNPs are large, rod-shaped complexes containing a core of NP, around which the RNA is helically wrapped. The vRNPs are the entities that enter the nucleus, and their nuclear import must be mediated by nuclear localization sequences (NLSs) exposed on the vRNPs. NP contains at least two putative NLSs, one at the N-terminus (NLS1) and one in the middle (NLS2) of the protein. These NP NLSs have been shown to mediate the nuclear import of recombinant NP molecules. However, it remains to be determined which NLS mediates the nuclear import of influenza vRNP complexes.