A review of influenza haemagglutinin receptor binding as it relates to pandemic properties

Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, United Kingdom.
Vaccine (Impact Factor: 3.62). 06/2012; 30(29):4369-76. DOI: 10.1016/j.vaccine.2012.02.076
Source: PubMed


Haemagglutinin is a determinant of many viral properties, and successful adaptation to a human-like form is thought to be an important step toward pandemic influenza emergence. The availability of structurally distinct sialic acid linked receptors in the sites of human and avian influenza infection are generally held to account for the differences observed, but the relevance of other selection pressures has not been elucidated. There is evidence for genetic and structural constraints of haemagglutinin playing a role in restricting haemagglutinin adaptation, and also for differences in the selection pressure to alter binding, specifically when considering virus replication within host compared to transmission between hosts. Understanding which characteristics underlie such adaptations in humans is now possible in greater detail by using glycan arrays. However, results from these assays must also interpreted in context of an as yet still to be determined detailed knowledge of the structural diversity of sialic acids in the human respiratory tract. A clearer understanding of the evolutionary benefits conveyed by different haemagglutinin properties would have substantial impact and would affect the risk we allocate to viral propagation in different species, such as swine and poultry. Relevant to the H5N1 threat, current evidence also suggests that mortality associated with any emergent pandemic from current strains may be reduced if haemagglutinin specificity changes, further emphasising the importance of understanding how and if selection pressures in the human will cause such an alteration.

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    • "Upon entering the respiratory tract, the influenza A virus HA surface protein binds to sialic acid-containing receptors on lung epithelial cells to initiate viral replication in the host cell. The NA surface protein cleaves the sialic acid-HA bond to release the viral capsule from the infected cell surface [46]. Thus, while the NA receptor is crucial for continued infection of epithelial cells, the goal of influenza vaccination is to neutralize the HA surface protein and prevent further infection. "
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    Vaccine 07/2015; 33(36). DOI:10.1016/j.vaccine.2015.06.101 · 3.62 Impact Factor
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    • "Hemagglutinin (HA), one of the major surface glycoprotein recognizes and attaches to sialic acid on the cell surface as the receptor for AIV (Webster et al., 1992). Thus the HA-receptor binding specificity determines the viral tropism and host range (Suzuki et al., 2000; Wilks et al., 2012). HA is also one of the major viral proteins responsible for inducing neutralizing antibody and provides protection from AIV infection ( Kostolansk´y et al., 2000; Gao et al., 2006; Swayne, 2009; Varečková et al., 2013). "
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