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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    ABSTRACT: Despite the high success of protection against several infectious diseases through effective vaccines, some sub-populations have been observed to respond poorly to vaccines, putting them at increased risk for vaccine-preventable diseases. In particular, the limited data concerning the effect of obesity on vaccine immunogenicity and efficacy suggests that obesity is a factor that increases the likelihood of a poor vaccine-induced immune response. Obesity occurs through the deposition of excess lipids into adipose tissue through the production of adipocytes, and is defined as a body-mass index (BMI)≥30kg/m(2). The immune system is adversely affected by obesity, and these "immune consequences" raise concern for the lack of vaccine-induced immunity in the obese patient requiring discussion of how this sub-population might be better protected. Copyright © 2015. Published by Elsevier Ltd.
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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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    Full-text · Article · Jan 2015 · Journal of Virological Methods
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    • "This finding is in agreement with the previous study that the addition of T-705, which is a chemical that inhibits viral replication, to MDCK cells infected with the influenza A/PR/8/34 strain is effective only when it is administered within 4 hours after infection [39]. Furthermore, it provides partial explanation for the decreased Oseltamivir efficacy administered later than the first 12 hours of fever onset [36], which can be mimicked when we chose a larger degree of perturbation. "
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    ABSTRACT: There is a strong need to develop novel strategies in using antiviral agents to efficiently treat influenza infections. Thus, we constructed a rule-based mathematical model that reflects the complicated interactions of the host immunity and viral life cycle and analyzed the key controlling steps of influenza infections. The main characteristics of the pandemic and seasonal influenza strains were estimated using parameter values derived from cells infected with Influenza A/California/04/2009 and Influenza A/NewCaledonia/20/99, respectively. The quantitative dynamics of the infected host cells revealed a more aggressive progression of the pandemic strain than the seasonal strain. The perturbation of each parameter in the model was then tested for its effects on viral production. In both the seasonal and pandemic strains, the inhibition of the viral release (kC ), the reinforcement of viral attachment (kV ), and an increased transition rate of infected cells into activated cells (kI ) exhibited significant suppression effects on the viral production; however, these inhibitory effects were only observed when the numerical perturbations were performed at the early stages of the infection. In contrast, combinatorial perturbations of both the inhibition of viral release and either the reinforcement of the activation of infected cells or the viral attachment exhibited a significant reduction in the viral production even at a later stage of infection. These results suggest that, in addition to blocking the viral release, a combination therapy that also enhances either the viral attachment or the transition of the infected cells might provide an alternative for effectively controlling progressed influenza infection.
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