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.
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.
Influenza A/NP: timer
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).
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.
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