Influenza Nucleoprotein / NP

Influenza virus NP is a major structural protein in Influenza virus particles and has multiple functions in the viral infectious cycle. Nucleoprotein (NP) is major component of the ribonucleoprotein complex and a critical factor in the viral infectious cycle in switching influenza virus RNA synthesis from transcription mode to replication mode. NP binds RNA with high affinity in a sequence-independent manner. Isolated influenza A virus nucleoprotein exists in an equilibrium between monomers and trimers while the wild type (wt) nucleoprotein is trimers. The trimers bind RNA with high affinity but remain trimmers, whereas the monomers polymerise onto RNA forming nucleoprotein-RNA complexes.

 

Influenza Nucleoprotein Structure

In Influenza A, Nucleoprotein is composed of a head and a body domain and a tail loop/ linker region. The head domain is more conserved than the body domain. NP proteins assume the overall shape of a crescent with a head and a body domain. In between the two domains is a deep groove enriched for basic amino acid residues and thus may function as the RNA-binding site.
Structure of Influenza D NP is a tetramer.

  • Neuraminidase structure, trtramer

    Influenza A/NP: timer

  • Neuraminidase stalk length

    Influenza D/NP: tetramer

Here is the illustration of functional domains of NP.

Sub-fragments of NP identified as capable of binding RNA (blue), NP (green) or PB2 (yellow) are indicated on a linear representation of the NP molecule. Numbers refer to the amino acid co-ordinates. Also indicated is a C-terminal acidic region (red), which acts as a repressor of PB2 and NP binding. Black bars indicate regions shown to be important for binding the cellular polypeptides actin, BAT1/UAP56, importin α (NLS I) and/or function as nuclear localization signals (NLS I and II) or as a cytoplasmic accumulation signal (CAS).

Influenza Neuraminidase Function

Neuraminidase (NA) has several functions in virus replication and infection:
• Virus Entry
• Receptor Binding
• Virus Internalization
• Catalytic Activity
• NA Substrate Specificity

Rather than just a sialidase that facilitates virus release from infected cells, the NA is a complicated multifunctional protein with an important role at many stages of the infectious process. While the NA is the main target for current antiviral therapies, recent approaches to new influenza therapy include targeting the HA with monoclonal antibodies. However, given the NA also has the capacity to bind receptors, there needs to be caution in this approach, as it is possible that compensating mutations in the NA may allow escape from inhibition of the HA.

 

Influenza Neuraminidase Reference

• Y.A. Shtyrya.Influenza Virus Neuraminidase: Structure and Function.Acta Naturae. 2009 Jul; 1(2): 26–32.
• Russell R.J.. The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design. Nature. 2006;44:45–49
• Julie L. McAuley.Influenza Virus Neuraminidase Structure and Functions.Front. Microbiol., 29 January 2019
• Feng Wen.Influenza Neuraminidase: Underrated Role in Receptor Binding.VOLUME 27, ISSUE 6, P477-479, JUNE 01, 2019

Influenza Virus Antigen Information