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The influenza virus polymerase complex is essential for directing virus replication inside the host cell's nucleus. The viral polymerase complex consists of three sub units, PA,PB1, and PB2 [7]. The polymerase complex directs both, viral RNA replication and viral genome transcription. Additionally, the complex can steal 5' RNA primers from host mRNAs during transcription of viral RNA [10]. NP has been found to have substantial regulatory interaction with PB1 and PB2. The NP interaction with PB2 is host specific and depends on the amino acid sequence found in the C-terminal tail loop region. Thus, the direct interaction between NP and PB2 may be the switch between viral RNA replication and transcription [6].

Importin α is a mediator protein that interacts with hundreds of different proteins in eukaryotic cells to ensure transport across the nuclear envelope through the nuclear pores. During early stages of infection, the NP is largely concentrated in the nucleus, importing viral RNA scripts for transcription and replication. The entrance of NP into the nucleus is guaranteed by the NP interaction with Importin α. [[Image:NP functional subunits.jpg]]

After the viral RNA scripts have been replicated, NP shuttles out of the nucleus by associating with CRM1 (chromosomal maintenance 1), also known as exportin [12]. In this later stage of infection, the concentration of NP in the cytoplasm outweighs the concentration of NP inside the nucleus. It is unknown if this is the case because the nuclear localization signals (NLS) are turned off or because the NLS are overwhelmed by the cytoplasmic accumulation signal (CAS), which describes the interaction between NP and the host cell cytoskeleton [1].

During the late stages of the infection, the CAS region on NP acts as a cytoplasmic retention signal by tethering the nucleoprotein to the cytoskeleton. The binding between NP and F-actin was confirmed in vitro and exhibited an affinity of ~1µM with a 1:1 stoicheometry NP:F-actin [12].

During packaging and assembly of new viral particles, the M1 protein (matrix protein 1 of influenza A) mediates the encapsidation of RNPs into the viral envelope. This interaction is critical for successful assembly of functional virus progeny and is characterized by direct protein-protein interaction between M1 and NP, which is stabilized by M1 simultaneously binding to the NP-bound RNA [1].

The influenza nucleoprotein in each strain features a fingerprint phosphorylation profile, which undergoes subtle changes during the course of a viral replication cycle. The phosphorylation profile is thought to be responsible for the diverse yet specific NP interactions at different stages in the replication cycle. Only serine residues have been found to be phosphorylated or dephosphorylated in NP. The phosphorylation profile of NP seems to be majorly influenced by the host cell's protein kinase C (PKC). In vitro inhibition of PKC by the phorbol ester 12-O-tetradecanolyphorbol 13-acetate or isoquinoline sulphonamide H7 resulted in significant phosphorylation changes in NP, proving the key role a correct NP phosphorylation profile plays in successful viral replication [5].