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.
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ABSTRACT: In December, 2007, a family cluster of two individuals infected with highly pathogenic avian influenza A (H5N1) virus was identified in Jiangsu Province, China. Field and laboratory investigations were implemented immediately by public-health authorities. Epidemiological, clinical, and virological data were collected and analysed. Respiratory specimens from the patients were tested by reverse transcriptase (RT) PCR and by viral culture for the presence of H5N1 virus. Contacts of cases were monitored for symptoms of illness for 10 days. Any contacts who became ill had respiratory specimens collected for H5N1 testing by RT PCR. Sera were obtained from contacts for H5N1 serological testing by microneutralisation and horse red-blood-cell haemagglutinin inhibition assays. The 24-year-old index case died, and the second case, his 52-year-old father, survived after receiving early antiviral treatment and post-vaccination plasma from a participant in an H5N1 vaccine trial. The index case's only plausible exposure to H5N1 virus was a poultry market visit 6 days before the onset of illness. The second case had substantial unprotected close exposure to his ill son. 91 contacts with close exposure to one or both cases without adequate protective equipment provided consent for serological investigation. Of these individuals, 78 (86%) received oseltamivir chemoprophylaxis and two had mild illness. Both ill contacts tested negative for H5N1 by RT PCR. All 91 close contacts tested negative for H5N1 antibodies. H5N1 viruses isolated from the two cases were genetically identical except for one non-synonymous nucleotide substitution. Limited, non-sustained person-to-person transmission of H5N1 virus probably occurred in this family cluster.The Lancet 05/2008; 371(9622):1427-34. · 39.06 Impact Factor
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ABSTRACT: Pandemic influenza requires interspecies transmission of an influenza virus with a novel hemagglutinin (HA) subtytpe that can adapt to its new host through either reassortment or point mutations and transmit by aerosolized respiratory droplets. Two previous pandemics of 1957 and 1968 resulted from the reassortment of low pathogenic avian viruses and human subtypes of that period; however, conditions leading to a pandemic virus are still poorly understood. Given the endemic situation of avian H9N2 influenza with human-like receptor specificity in Eurasia and its occasional transmission to humans and pigs, we wanted to determine whether an avian-human H9N2 reassortant could gain respiratory transmission in a mammalian animal model, the ferret. Here we show that following adaptation in the ferret, a reassortant virus carrying the surface proteins of an avian H9N2 in a human H3N2 backbone can transmit efficiently via respiratory droplets, creating a clinical infection similar to human influenza infections. Minimal changes at the protein level were found in this virus capable of respiratory droplet transmission. A reassortant virus expressing only the HA and neuraminidase (NA) of the ferret-adapted virus was able to account for the transmissibility, suggesting that currently circulating avian H9N2 viruses require little adaptation in mammals following acquisition of all human virus internal genes through reassortment. Hemagglutinin inhibition (HI) analysis showed changes in the antigenic profile of the virus, which carries profound implications for vaccine seed stock preparation against avian H9N2 influenza. This report illustrates that aerosolized respiratory transmission is not exclusive to current human H1, H2, and H3 influenza subtypes.Proceedings of the National Academy of Sciences 05/2009; 106(18):7565-70. · 9.74 Impact Factor
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ABSTRACT: Human H3 strains of influenza A virus preferentially bind cell-surface oligosaccharides containing the sequence NeuAc alpha 2,6Gal, while avian influenza strains preferentially recognize the sequence NeuAc alpha 2,3Gal. The distribution of these two types of sialic acid linkages on host respiratory epithelium, the target of influenza infection, may be a factor in the selection of the different receptor specificities observed in human and avian influenza strains. To examine the distribution of these two structures on human tracheal epithelial cells, two sialic acid specific lectins were used. The Sambucus nigra lectin (SNA), which recognizes the sequence NeuAc alpha 2,6Gal/GalNac, primarily binds to the surface of the ciliated tracheal epithelial cells, and only weakly binds to mucins in the surface goblet cells. In contrast, the Maackia amurensis lectin (MAL), which is specific for the NeuAc alpha 2,3Gal sequence, binds strongly to mucus droplets in goblet cells, but not to the surface of ciliated cells. Thus, human ciliated tracheal cells appear to contain sialyloligosaccharides preferentially recognized by human influenza strains. These findings suggest that human H3 influenza strains may have evolved a receptor specificity which favors binding to ciliated cells, and minimizes binding inhibition by respiratory mucus.Acta histochemica. Supplementband 02/1990; 40:35-8.