The HA is a homotrimeric rod-shaped type I transmembrane glycoprotein . Each monomer unit has a length of 540-550 amino acids that contains an N-terminal signal sequence and a C-terminal membrane anchor [50, 51]. HA monomers are synthesized as precursors (HA0) that undergo proteolytic cleavage to generate disulfide-bonded HA1 and HA2 polypeptide chains before activation [52, 53]. Most IAV contain a single basic amino acid residue (arginine, rarely lysine) at the cleavage site and are classified as LPAIV. Some H5 and H7 subtypes possess multiple basic amino acids that are cleaved by ubiquitous proteases that recognize the multibasic motif and are classified as highly pathogenic avian influenza viruses (HPAIV) .
The HA0 of LPAIV is cleaved by trypsin-like enzymes at the cell surface or after the release of the virus from the cell . Trypsin-like proteases are secreted by the epithelial cells lining the respiratory and digestive tract . The HA of HPAIV is cleaved by ubiquitous proteases such as furin-like enzymes resulting in systemic infections [55, 56]. Several studies have shown that HPAIV emerge from LPAIV as a result of modification in the amino acid composition at the cleavage site . The mechanisms of cleavage site alteration include the acquisition of basic amino acids due to polymerase slippage, recombination of the HA gene with other viral segments or ribosomal RNAs, and insertions [56-58].
The pivotal roles of the HA are the attachment to the host cell receptor and fusion activities . HA binds to the sialic acid (SA) present on the surface of the host glycoproteins and glycolipids . The head of the HA is entirely formed by HA1 residues and contains the receptor binding site (RBS) . Each membrane-proximal “stem” region is assembled from the HA2 and part of the HA1 and holds the fusion machinery . The conformation of the SA in the host cells determines the preference of the IAV binding; thus, avian and equine influenza viruses preferentially bind to SA attached to the penultimate galactose sugar by an 2,3 linkage (SA2,3Gal), whereas human-adapted and swine viruses prefer SA with an 2,6 linkage (SA2,6Gal) . Differences in binding specificities between IAV can be matched with the glycan distribution on infection sites . The SA2,6 is abundantly present in the trachea, and bronchus of the human upper respiratory tract, and in the type I pneumocytes in the lower respiratory tract . The alveolar type II pneumocytes express predominantly SA2,3, limiting transmissibility of avian influenza viruses in humans [60, 62]. In contrast, the gut epithelial cells of ducks hold mostly SA2,3; although, recent studies have shown the presence of SA2,6 in ciliated cells of the trachea and in the colon [63, 64]. Chickens express SA2,6Gal and SA2,3Gal in the respiratory and intestinal tract . Similarly, both SA2,3Gal and SA2,6Gal are displayed on tracheal and intestinal cells of quail, turkey, pheasant, and guinea fowl, and might play a role in the adaptation of avian influenza viruses to mammalian species [63, 66]. The scarcity of receptors in the upper human
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Essay Sauce, HA – homotrimeric rod-shaped type I transmembrane glycoprotein. Available from:<https://www.essaysauce.com/science-essays/ha-homotrimeric-rod-shaped-type-i-transmembrane-glycoprotein/> [Accessed 21-07-19].