Influenza Neuraminidase / NA

Influenza neuraminidase is on the surface of influenza viruses that enables the virus to be released from the host cell. Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins and are required for influenza virus replication. In addition to the mutations that arise due to antigenic drift, the NA of influenza A viruses (IAVs) can exist in different forms.Based on HA and NA antigenicity using serologic tests with hyperimmune sera, there have been a total of 16 HA (H1-16) and 9 NA (N1-9) subtypes identified in birds.Nine subtypes of influenza A NA are divided into two phylogenic groups. The first group consists of the neuraminidases of N1, N4, N5 and N8 subtypes, and the second one consists of N2, N3, N6 N7 and N9 subtypes.These are expressed in numerous combinations of viruses isolated from aquatic avian species, and an additional two combinations, H17N10 and H18N11, have been identified in bats

 

Influenza Neuraminidase Structure

The neuraminidase (NA) assembles as a tetramer of four identical polypeptides.The four monomers fold into four distinct structural domains:
• cytoplasmic tail
• transmembrane region
• stalk
• catalytic head

NA tetramer exists in local clusters on the virion surface or as isolated spikes surrounded by HA. Reduced stalk length may impact the ability of NA to contact sialic acids on mucins or cellular receptors as neighboring HA may sterically hinder its approach. Depending on the length of the stalk region, the NA may protrude slightly more or less above the viral envelope than the HA, which may influence the overall enzymatic activity of the virus.

  • Neuraminidase structure, trtramer

    Picture 1: NA structure

  • Neuraminidase stalk length

    Picture 2: Stalk length of NA

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