H7 Birdflu virus outbreak in Australia

Influenza viruses of gallinaceous poultry and wild aquatic birds usually have distinguishable receptor-binding properties. Here we used a panel of synthetic sialylglycopolymers and solid-phase receptor-binding assays to characterize receptor-binding profiles of about 70 H7 influenza viruses isolated from aquatic birds, land-based poultry, and horses in Eurasia and America. Unlike typical duck influenza viruses with non-H7 hemagglutinin (HA), all avian H7 influenza viruses, irrespective of the host species, displayed a poultry-virus-like binding specificity, i.e., preferential binding to sulfated oligosaccharides Neu5Acα2-3Galβ1-4(6-O-HSO3)GlcNAc and Neu5Acα2-3Galβ1-4(Fucα1-3)(6-O-HSO3)GlcNAc. This phenotype correlated with the unique amino acid sequence of the amino acid 185 to 189 loop of H7 HA and seemed to be dependent on ionic interactions between the sulfate group of the receptor and Lys193 and on the lack of sterical clashes between the fucose residue and Gln222. Many North American and Eurasian H7 influenza viruses displayed weak but detectable binding to the human-type receptor moiety Neu5Acα2-6Galβ1-4GlcNAc, highlighting the potential of H7 influenza viruses for avian-to-human transmission. Equine H7 influenza viruses differed from other viruses by preferential binding to the N-glycolyl form of sialic acid. Our data suggest that the receptor-binding site of contemporary H7 influenza viruses in aquatic and terrestrial birds was formed after the introduction of their common precursor from ducks to a new host, presumably, gallinaceous poultry. The uniformity of the receptor-binding profile of H7 influenza viruses in various wild and domestic birds indicates that there is no strong receptor-mediated host range restriction in birds on viruses with this HA subtype. This notion agrees with repeated interspecies transmission of H7 influenza viruses from aquatic birds to poultry.

The major natural reservoirs of influenza A viruses are wild aquatic birds of the orders Anseriformes (ducks, geese, and swans) and Charadriiformes (gulls, terns, and waders), which harbor viruses of all 16 hemagglutinin (HA) and 9 neuraminidase (NA) antigenic subtypes currently known. Dabbling ducks (Anatinae), such as mallards and teals, carry almost all subtypes and show particularly high virus isolation rates, suggesting a unique role of these species in the persistence of influenza viruses in nature (for reviews, see references 144146, and 64). Occasionally, influenza viruses of aquatic birds infect other birds and mammals, adapt to efficiently replicate and transmit in the new species, and continue to circulate, forming new stable host-specific virus lineages. All known lineages of influenza A viruses in land-based birds and mammals are believed to originate from the viruses of wild aquatic birds. Adaptation of influenza viruses to their sialic acid-containing receptors in a new host species is often required for successful interspecies transmission. Thus, avian influenza viruses bind to receptors containing terminal sialyl-galactosyl residues linked by an α2-3 linkage (Neu5Acα2-3Gal), whereas swine and human viruses bind to receptors which contain terminal α2-6-linked sialyl-galactosyl moieties (Neu5Acα2-6Gal) (1018273235444750), and a corresponding switch in the receptor specificity of the avian precursor is essential for the emergence of new stable virus lineages in humans and pigs (reviewed in references 125, and 34).

Based on early data (1035), it was assumed that all avian influenza viruses have similar receptor-binding specificities and, therefore, that there is no significant receptor-mediated restriction on viral interspecies transmission in birds. The first evidence arguing against this concept was obtained in a study on H5N1 viruses from Hong Kong isolated in 1997, when virus isolates from poultry and humans were found to have a lower receptor binding affinity and a lower neuraminidase activity than closely related viruses of aquatic birds (33). In addition, analysis of the HA and NA sequences of H5 and H7 influenza viruses from various avian species revealed that poultry influenza viruses often differ from duck influenza viruses by additional N-linked glycans at the top of HA and by large deletions in the stalk of NA (233). Furthermore, the H9N2 viruses widely circulating in poultry in Eurasia were found to differ significantly in their receptor specificity from H9N2 viruses of other evolutionary lineages. In particular, these Eurasian poultry influenza viruses displayed good binding to α2-6-linked sialic acids (3753). Studies on expression of sialic acids in intestinal and respiratory epithelia of different birds revealed substantial host-specific distinctions, among them, expression of both Neu5Acα2-3Gal- and Neu5Acα2-6Gal-terminated sialyloligosaccharides in chicken and quail, in contrast to ducks, which mainly contain Neu5Acα2-3Gal in their intestinal epithelium (16192329,4963). Taken together, these findings indicated that influenza viruses perpetuated in different birds can have different receptor specificities owing to distinctions in the sialic acid receptors in these avian species.

Subsequent detailed studies on viral receptor-binding specificity revealed that preferential binding to terminal Neu5Acα2-3Gal disaccharide is shared by the majority of avian viruses; however, viruses adapted to ducks, gulls, and land-based gallinaceous poultry differ in their ability to recognize the subterminal saccharides of Neu5Acα2-3Gal-terminated receptors (reviewed in references 34 and 43). Duck influenza viruses of various HA subtypes (H1 to H5, H9 to H11) preferentially bound to receptors with type 1 and type 3 oligosaccharide sequences, i.e., having the β1-3 linkage between the terminal Neu5Acα2-3Gal moiety and the penultimate sugar residue such as Neu5Acα2-3Galβ1-3GlcNAc (SLec) and Neu5Acα2-3Galβ1-3GalNAcα (STF). Sulfation at the 6-OH group of the subterminal GlcNAc had little effect on binding of duck influenza viruses, whereas fucosylation of this residue reduced the binding significantly (15172021). In contrast to duck influenza viruses, the H4, H6, H13, and H14 subtype viruses isolated from gulls showed high-avidity binding to fucosylated sialyloligosaccharides Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAc (SLex) and Neu5Acα2-3Galβ1-3(Fucα1-4)GlcNAc (SLea) (1767). Influenza viruses with HA subtypes H5, H7, and H9 are commonly reported in terrestrial gallinaceous poultry (79). The common properties shared by these poultry-adapted viruses are (i) preferential binding to receptors with type 2 sequences having a β1-4 bond between the Neu5Acα2-3Gal moiety and the next sugar residue, such as Neu5Acα2-3Galβ1-4GlcNAc (3′SLN) and (ii) particularly strong binding to the corresponding sulfated analogues Neu5Acα2-3Galβ1-4(6-O-HSO3)GlcNAc (Su-3′SLN) and Neu5Acα2-3Galβ1-4(Fucα1-3)(6-O-HSO3)GlcNAc (Su-SLex) (172021).

In the case of H5 and H9 subtypes, virus strains with both duck-virus-like and poultry-virus-like receptor phenotypes were identified in corresponding avian species (172021). In contrast to these relatively extensive analyses of H5 and H9 influenza viruses, previous studies on receptor specificity of H7 influenza viruses were limited to a few virus strains from North American and Eurasian poultry. All tested H7 influenza viruses displayed a poultry-virus-like receptor specificity, and some of them showed the ability to bind to human-type receptors (42068). To fill the gap in current knowledge on the receptor specificity of H7 influenza viruses, especially those circulating in wild aquatic birds, here we analyzed a large collection of viruses from various host species.


Author: Gilbert Tan TS

IT expert with more than 20 years experience in Apple, Andriod and Windows PC. Interests include hardware and software, Internet and multimedia. An experienced Real Estate agent, Insurance agent, and a Futures trader.

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