A review of influenza haemagglutinin receptor binding as it relates to pandemic properties
ABSTRACT 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.
- SourceAvailable from: Yung-Yi Chen Mosley
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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). "
ABSTRACT: DNA vaccine coding for infectious bursal disease virus (IBDV) polyprotein gene and that for avian influenza virus (AIV) hemagglutinin (HA) gene have been shown to induce immunity and provide protection against the respective disease. The present study was carried out to determine whether an IBDV polyprotein gene-based DNA fused with AIV HA gene could trigger immune response to both IBDV and AIV. After transfection, VP2 and HA were detected in the cytoplasm and at cell membrane, respectively, by immunofluorescent antibody double staining method, suggesting the fusion strategy did not affect the location of protein expression. VP4 cleavage between VP2 and HA was confirmed by Western blot, indicating the fusion strategy did not affect VP4 function in transfected cells. After vaccination in chickens, the DNA construct VP24-HA/pcDNA induced ELISA and virus neutralizing antibodies against VP2 and hemagglutination inhibition antibody against the HA subtype. The results indicated that a single plasmid construct carrying IBDV VP243 gene-based DNA fused with AIV HA gene can elicit specific antibody responses to both IBDV and AIV by DNA vaccination.Journal of Virological Methods 01/2015; 211. DOI:10.1016/j.jviromet.2014.10.011 · 1.88 Impact Factor
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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 . Furthermore, it provides partial explanation for the decreased Oseltamivir efficacy administered later than the first 12 hours of fever onset , which can be mimicked when we chose a larger degree of perturbation. "
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.PLoS ONE 07/2013; 8(7):e68235. DOI:10.1371/journal.pone.0068235 · 3.23 Impact Factor
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- "In general terms, the HA of avian IAV prefers Neu5Acα2-3Gal-containing receptors, which are expressed throughout the digestive and respiratory tracts of birds. In contrast, human IAV bind receptors containing Neu5Acα2-6Gal, the predominant linkage expressed by epithelial cells of the human upper airways (reviewed in Wilks et al., 2012). In the 20th century, three subtypes of human IAV (H1N1, H2N2, and H3N2) evolved from pandemic viruses of 1918, 1957, and 1968, respectively, and all originated from avian viruses that transmitted to humans. "
ABSTRACT: Innate immunity represents the first line of defense against pathogens and plays key roles in activation and orientation of the adaptive immune response. The innate immune system comprises both a cellular and a humoral arm. Components of the humoral arm include soluble pattern recognition molecules (PRMs) that recognize pathogen-associated molecular patterns and initiate the immune response in coordination with the cellular arm, therefore acting as functional ancestors of antibodies. The long pentraxin PTX3 is a prototypic soluble PRM that is produced at sites of infection and inflammation by both somatic and immune cells. Gene targeting of this evolutionarily conserved protein has revealed a non-redundant role in resistance to selected pathogens. Moreover, PTX3 exerts important functions at the crossroad between innate immunity, inflammation, and female fertility. The human PTX3 protein contains a single N-glycosylation site that is fully occupied by complex type oligosaccharides, mainly fucosylated and sialylated biantennary glycans. Glycosylation has been implicated in a number of PTX3 activities, including neutralization of influenza viruses, modulation of the complement system, and attenuation of leukocyte recruitment. Therefore, this post translational modification might act as a fine tuner of PTX3 functions in native immunity and inflammation. Here we review the studies on PTX3, with emphasis on the glycan-dependent mechanisms underlying pathogen recognition and crosstalk with other components of the innate immune system.Frontiers in Immunology 01/2012; 3:407. DOI:10.3389/fimmu.2012.00407