HA – homotrimeric rod-shaped type I transmembrane glycoprotein

The HA is a homotrimeric rod-shaped type I transmembrane glycoprotein [15]. 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[1]. 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) [1].
The HA0 of LPAIV is cleaved by trypsin-like enzymes at the cell surface or after the release of the virus from the cell [54]. Trypsin-like proteases are secreted by the epithelial cells lining the respiratory and digestive tract [51]. 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 [51]. 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 [59]. HA binds to the sialic acid (SA) present on the surface of the host glycoproteins and glycolipids [60]. The head of the HA is entirely formed by HA1 residues and contains the receptor binding site (RBS) [44]. Each membrane-proximal “stem” region is assembled from the HA2 and part of the HA1 and holds the fusion machinery [59]. 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) [60]. Differences in binding specificities between IAV can be matched with the glycan distribution on infection sites [51]. 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 [61]. 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 [65]. 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 respiratory tract for avian influenza viruses limits cross-species transmission [62]. However, the species barrier might be overcome when infection with high viral loads occurs [60]. Effective maintenance and airborne transmission of IAV in new hosts require alterations in the HA binding properties [62]. For instance, the HA of the H7N9 virus causing infections in humans was able to bind to both receptors (SA2,3Gal and SA2,6Gal) by glycan arrays [67]. Alterations in certain amino acid positions in the RBS are responsible for the shift of H2 and H3 preference from avian to human receptors, which includes Gln222Leu and Gly228Ser [68]. Also, Asn182Lys has been associated with the occurrence of H5N1 cases in humans [69].

The interaction between the HA with the host receptor is not only limited by the linkage between the SA and the penultimate sugar residue, but also by the structure of the glycans, the length of the carbohydrate chain, branching pattern, as well as sulfation and fucosylation [1]. Another mechanism of modulation of the HA function is through glycosylation [70]. The HA protein contains N-glycans that are synthesized by the host cellular machinery; as a result, variations of the carbohydrates in the HA are host dependent [71]. There are conserved N-glycosylation sites among various HAs, while the location of the other sites differs between viruses [72]. Conservation of the glycosylation sites in the stem regions of the HA suggests important functional roles such as stabilization of the HA before fusion activation and transport of the HA to the cell surface [73, 74]. Previous research showed that H5 and H7 HAs isolated from chickens showed increased glycosylation and a deletion in the NA stalk as compared to duck viruses, which did not have a deletion and were not glycosylated [75].

Source: Essay UK - https://www.essay.uk.com/essays/science/ha-homotrimeric-rod-shaped-type-i-transmembrane-glycoprotein/

Not what you're looking for?

Search our thousands of essays:


About this resource

This Science essay was submitted to us by a student in order to help you with your studies.

  • Order a custom essay
  • Print this page
  • Search again

Word count:

This page has approximately words.



If you use part of this page in your own work, you need to provide a citation, as follows:

Essay UK, HA – homotrimeric rod-shaped type I transmembrane glycoprotein. Available from: <https://www.essay.uk.com/essays/science/ha-homotrimeric-rod-shaped-type-i-transmembrane-glycoprotein/> [21-05-19].

More information:

If you are the original author of this content and no longer wish to have it published on our website then please click on the link below to request removal:

Latest essays in this category:

Our free essays: