Influenza virus sialidase location

Electron micrograph experiments of influenza virus particles reveal that sialidase appears as numerous mushroom-shaped spikes on the surface of the virus [25,26]. The box-shaped head of the mushroom (100 x 100 x 60 A) is composed of a tetramer of identical sialidase subunits, centrally attached to a long, thin stalk with a hydrophobic region that embeds itself into the viral membrane. Each monomeric unit has one active site, located in pockets that occur on the upper surface of the mushroom-head tetramer and viewed as a distinct depression on the surface. 

The function of this conserved and repeated motif is as yet unknown. In the N9 influenza A virus sialidase (Air et al., 1987), the single Asp-box is located as part of a -pleated sheet polypeptide at the connections between the four protein... 

Viruses that contain amino acid substitutions in the sialidase that impart resistance to the developed inhibitors have been isolated from serial passage of virus in the presence of drug in cell culture and from the clinical setting (reviewed in McKimm-Breschkin 2000 Zambon and Hayden 2001 Cinatl et al. 2007a Reece 2007). In addition, influenza B virus variants with reduced drug sensitivity have been isolated from previously untreated patients (Hurt et al. 2006 Hatakeyama et al. 2007). The types of mutations that are observed are sub-type specific. The mutations present in variants isolated from clinical samples are shown in Table 1, and their locations within the sialidase active site are shown diagrammatically in Fig. 9. 

Figure 22.3 X-Ray crystal structure of influenza A virus N2 sialidase monomer with a-Neu5Ac (4) bound (PDB 2bat). (a) The monomeric subunit of the tetramer contains six four-stranded p-sheets arranged as in the blades of a propeller, (b) The active site, located close to the center of the monomer,...

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