Neuraminidase Protein of Influenza A H7N9 Virus (NA)

The neuraminidase (NA) protein is one of the two major surface glycoproteins found on the influenza A virus, including the H7N9 subtype. It plays a critical role in the viral life cycle by facilitating the release and spread of progeny virions from infected host cells. The NA protein achieves this by cleaving sialic acid residues from glycoproteins and glycolipids on the surface of host cells and newly formed viral particles[6][8]. The NA protein is a tetrameric enzyme embedded in the viral envelope. Each monomer consists of a globular head domain containing both an enzymatic active site (sialidase activity) and, in some subtypes like N9, an additional sialic acid binding site known as the hemadsorption (Hb) site[6]. In influenza A viruses, including H7N9, neuraminidase is encoded by one segment of their segmented negative-sense RNA genome[8]. The primary function is to cleave terminal sialic acids from cellular receptors to promote efficient release and spread of new virions after replication. Uniquely for N9 neuraminidases (as found in H7N9), there exists a secondary receptor-binding site distinct from its catalytic center. This allows NA not only to facilitate virus release but also to bind sialic acid-containing receptors directly[6]. This dual functionality may enhance binding to human-like receptors and could influence transmissibility between humans. The interplay between hemagglutinin (HA), which binds sialic acids for cell entry, and neuraminidase (NA), which removes them for exit, determines infectivity and transmission efficiency. For H7N9 viruses: Their NA has unusual kinetic properties that promote receptor binding via both its secondary Hb site and its active enzymatic site. These features may contribute to enhanced adaptation toward human hosts compared with other avian influenza viruses[6]. Such adaptations are considered important factors underlying pandemic potential. Like all influenza proteins, NA evolves rapidly due to antigenic drift—accumulation of mutations—which can affect drug sensitivity or immune recognition. Mutations within or near functional sites can alter substrate specificity or inhibitor susceptibility. Neuraminidase inhibitors such as oseltamivir target this protein; resistance can arise through mutations affecting drug-binding sites. Monitoring changes in NA structure/function is crucial for surveillance efforts aimed at pandemic preparedness.

Neuraminidase inhibition