Gambaryan, A. et al. Evolution of the receptor binding phenotype of influenza A (H5) viruses. Virology 344, 432-438

Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, 142782 Moscow, Russia.
Virology (Impact Factor: 3.32). 02/2006; 344(2):432-8. DOI: 10.1016/j.virol.2005.08.035
Source: PubMed


Receptor specificity of influenza A/H5 viruses including human 2003-04 isolates was studied. All but two isolates preserved high affinity to Sia2-3Gal (avian-like) receptors. However, two isolates (February, 2003, Hong Kong) demonstrated decreased affinity to Sia2-3Gal and moderate affinity to a Sia2-6Gal (human-like) receptors. These two viruses had a unique Ser227-Asn change in the hemagglutinin molecule. Thus, a single amino acid substitution can significantly alter receptor specificity of avian H5N1 viruses, providing them with an ability to bind to receptors optimal for human influenza viruses. Asian 2003-04 H5 isolates from chickens and humans demonstrated highest affinity to the sulfated trisaccharide Neu5Acalpha2-3Galbeta1-4(6-HSO3)GlcNAcbeta (Su-3'SLN) receptor but, in contrast to 1997 isolates, had increased affinity to fucosylated Su-3'SLN. American poultry H5 viruses also had increased affinity to Su-3'SLN. These data demonstrate that the genetic evolution of avian influenza A(H5N1) viruses is accompanied during adaptation to poultry by the evolution of their receptor specificity.

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Available from: Amanda Balish, Sep 29, 2015
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    • "In this study, comparison of the predicted amino acid sequences of HB10-MA and HB10 viruses demonstrated five substitutions involving four of the ten viral proteins. Mouseadapted HB10-MA virus acquired a S227N mutation within the binding site, and this position is considered to have a reduced binding affinity toward SA2, 3 Gal and an increased affinity toward SA2, 6 Gal (Gambaryan et al., 2006), it together with the removal of the 158N glycosylation (Yen et al., 2009), resulted in more-efficient viral replication in the upper respiratory tract of ferrets and serum antibody response. The PB2 gene is important for the virulence of HPAI H5N1 and H7N7 viruses and the transmission of H1N1/1918 virus (Hatta et al., 2001). "
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    ABSTRACT: It is reported that the H5N2 highly pathogenic avian influenza virus A/chicken/Hebei/1102/2010 (HB10) is a natural reassortant between circulating H5N1 and endemic H9N2 influenza viruses. To evaluate the potential of its interspecies transmission, the wild-type HB10 was adapted in mice through serial lung passages. Increased virulence was detectable in 5 sequential lung passages in mice and a highly virulent mouse-adapted strain (HB10-MA) with a 50% mouse lethal dose of 10(2.5) 50% egg infectious dose was obtained in 15 passages. The virulence and the replication efficiency of HB10-MA in mice were significantly higher than those of HB10 while HB10-MA grew faster and to significantly higher titers than HB10 in MDCK and A549 cells. Only five amino acid mutations in four viral proteins (HA-S227N, PB2-Q591K, PB2-D701N, PA-I554V and NP-R351K) of HB10-MA virus were found when compared with those of HB10, indicating that they may be responsible for the adaptation of the novel reassortant H5N2 avian influenza virus in mice with increased virulence and replication efficiency. The results in this study provide helpful insights into the pathogenic potential of novel reassortant H5N2 viruses to mammals that deserves further attentions.
    Veterinary Microbiology 06/2014; 172(3-4). DOI:10.1016/j.vetmic.2014.06.018 · 2.51 Impact Factor
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    • "We have studied the mechanisms by which these mutations alter receptor binding. We have used biolayer interferometry (BLI) to quantitate receptor binding by HAs identified in Southeast Asian clade 1 H5N1 human isolates (Gambaryan et al., 2006; Yamada et al., 2006) and in mutant clade 2.2 viruses that are endemic in Egypt. (Watanabe et al., 2011). "
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    ABSTRACT: Mutant H5N1 influenza viruses have been isolated from humans that have increased human receptor avidity. We have compared the receptor binding properties of these mutants with those of wild-type viruses, and determined the structures of their haemagglutinins in complex with receptor analogues. Mutants from Vietnam bind tighter to human receptor by acquiring basic residues near the receptor binding site. They bind more weakly to avian receptor because they lack specific interactions between Asn-186 and Gln-226. In contrast, a double mutant, Δ133/Ile155Thr, isolated in Egypt has greater avidity for human receptor while retaining wild-type avidity for avian receptor. Despite these increases in human receptor binding, none of the mutants prefers human receptor, unlike aerosol transmissible H5N1 viruses. Nevertheless, mutants with high avidity for both human and avian receptors may be intermediates in the evolution of H5N1 viruses that could infect both humans and poultry.
    Virology 05/2014; s 456–457(100):179–187. DOI:10.1016/j.virol.2014.03.008 · 3.32 Impact Factor
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    • "Some strains of the highly pathogenic H5N1 virus, such as A/Hong Kong/486/97 (HK486) or A/Duck/Hong Kong/200/01, show high binding affinity to SAα-2,3Gal but not SAα-2,6Gal. However, some other strains isolated from patients, such as A/Hong Kong/212/03 and A/Hong Kong/213/03 (HK213), can recognize both SAα-2,3Gal and SAα-2,6Gal.17,18 These findings implicate the ability of H5N1 virus, which preferentially binds to SAα-2,3Gal, to switch to SAα-2,6Gal if the virus is transmitted and begins to adapt to humans. "
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    ABSTRACT: The H5N1 influenza A virus that is currently circulating in Asia, Africa and Europe has resulted in persistent outbreaks in poultry with sporadic transmission to humans. Thus far, it is believed that H5N1 does not possess sufficient ability for human-to-human transmission and subsequent pandemic infection. Both receptor binding specificity and virus infectivity are key factors in determining whether influenza A virus becomes pandemic. The use of human viral isolates in various studies has helped to illustrate the changes in receptor binding specificity and virulence as a result of adaptation in humans. In this review, we highlight the important amino acids and domains of viral proteins related to receptor binding specificity that have been reported for humans and avians using mammalian models. Thus, this review will consolidate findings from studies that have shed light on the receptor binding and transmission characteristics of the H5N1 influenza virus, with the goal of improving our ability to predict the transmission efficiency or pandemic potential of new viral strains.
    Emerging Microbes and Infections 12/2013; 2(12). DOI:10.1038/emi.2013.89 · 2.26 Impact Factor
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