Influenza Virus Structure

Influenza virus structure

Influenza viruses are roughly spherical, although somewhat pleomorphic, particles, ranging from 80 to 120 nm in diameter. 1, 7 Figure 5presents a model of the overall structure of the influenza virus. A characteristic feature of influenza virus particles is their external layer ofapproximately 500 spike-like projections. These spikes represent the envelope glycoproteins HA (which has a rod-like shape) and NA (which is mushroom-shaped). 7 The HA spike is a trimer, consisting of three individual HA monomers, 8 while the NA spike is a tetramer. 9,10 HA is about four times more abundant than NA.

Figure 5Model of influenza virus.

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The viral envelope proteins

The major envelope glycoprotein HA is synthesized in the infected cell as a single polypeptide chain (HA0) with a length of approximately 560 amino acid residues, which is subsequently cleaved into two subunits, HA1 and HA2. 1, 8 These subunits remain covalently linked to one another through disulphide bonds. Cleavage of HA0 is essential for the molecule to be able to mediate membrane fusion between the viral envelope and the host cell membrane, as discussed in more detail below. HA belongs to the first proteins for which the entire three-dimensional structure has been elucidated. Treatment of whole virions with the enzyme bromelain, which clips the polypeptide chain just above the viral membrane, releases a water-soluble fragment of the HA spike, commonly referred to as BHA. The ectodomain of HA of A/Aichi/2/68 (H3N2) virus, related to the Hong Kong pandemic virus of 1968, has thus been crystallized and subjected to X-ray analysis. 8,11 Figure 6 presents a representation of the 3D structure of HA based on this pioneering X-ray crystallographic structure determination.

Figure 6The three-dimensional structure of the influenza haemagglutinin (HA). The HA monomer (left) and trimer (right) are shown. In the monomer, the globular HA1 subunit is shown in dark blue, the HA2 subunit in light blue, with the “fusion peptide” in red. The receptor-binding site of HA1 is located at the tip of the molecule. This figure was produced by André van Eerde (University of Groningen), using MOLSCRIPT, on the basis of the co-ordinate file from the Protein Data Bank, code 3HMG.source: Weis WI et al. Refinement of the influenza virus hemagglutinin by simulated annealing. J Molec Biol 1990; 212: 737–761.