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Receptor binding profiles of avian influenza virus hemagglutinin subtypes on human cells as a predictor of pandemic potential.

ABSTRACT: The host adaptation of influenza virus is partly dependent on the sialic acid (SA) isoform bound by the viral hemagglutinin (HA). Avian influenza viruses preferentially bind the ?-2,3 SA and human influenza viruses the ?-2,6 isoform. Each isoform is predominantly associated with different surface epithelial cell types of the human upper airway. Using recombinant HAs and human tracheal airway epithelial cells in vitro and ex vivo, we show that many avian HA subtypes do not adhere to this canonical view of SA specificity. The propensity of avian viruses to adapt to human receptors may thus be more widespread than previously supposed.

SUBMITTER: Shelton H

PROVIDER: S-EPMC3028872 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Receptor binding profiles of avian influenza virus hemagglutinin subtypes on human cells as a predictor of pandemic potential.

Shelton Holly H Ayora-Talavera Guadalupe G Ren Junyuan J Loureiro Silvia S Pickles Raymond J RJ Barclay Wendy S WS Jones Ian M IM

Journal of virology 20101124 4

The host adaptation of influenza virus is partly dependent on the sialic acid (SA) isoform bound by the viral hemagglutinin (HA). Avian influenza viruses preferentially bind the α-2,3 SA and human influenza viruses the α-2,6 isoform. Each isoform is predominantly associated with different surface epithelial cell types of the human upper airway. Using recombinant HAs and human tracheal airway epithelial cells in vitro and ex vivo, we show that many avian HA subtypes do not adhere to this canonica ...[more]

PMID: 21106732

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Project description:H7N9 avian influenza viruses (AIVs) continue to evolve and remain a huge threat to human health and the poultry industry. Previously, serially passaging the H7N9 A/Anhui/1/2013 virus in the presence of homologous ferret antiserum resulted in immune escape viruses containing amino acid substitutions alanine to threonine at residues 125 (A125T) and 151 (A151T) and leucine to glutamine at residue 217 (L217Q) in the hemagglutinin (HA) protein. These HA mutations have also been found in field isolates in 2019. To investigate the potential threat of serum escape mutant viruses to humans and poultry, the impact of these HA substitutions, either individually or in combination, on receptor binding, pH of fusion, thermal stability, and virus replication were investigated. Our results showed the serum escape mutant formed large plaques in Madin-Darby canine kidney (MDCK) cells and grew robustly in vitro and in ovo They had a lower pH of fusion and increased thermal stability. Of note, the serum escape mutant completely lost the ability to bind to human-like receptor analogues. Further analysis revealed that N-linked glycosylation, as a result of A125T or A151T substitutions in HA, resulted in reduced receptor-binding avidity toward both human and avian-like receptor analogues, and the A125T+A151T mutations completely abolished human-like receptor binding. The L217Q mutation enhanced the H7N9 acid and thermal stability while the A151T mutation dramatically decreased H7N9 HA thermal stability. To conclude, H7N9 AIVs that contain A125T+A151T+L217Q mutations in the HA protein may pose a reduced pandemic risk but remain a heightened threat for poultry.IMPORTANCE Avian influenza H7N9 viruses have been causing disease outbreaks in poultry and humans. We previously determined that propagation of H7N9 virus in virus-specific antiserum gives rise to mutant viruses carrying mutations A125T+A151T+L217Q in their hemagglutinin protein, enabling the virus to overcome vaccine-induced immunity. As predicted, these immune escape mutations were also observed in the field viruses that likely emerged in the immunized or naturally exposed birds. This study demonstrates that the immune escape mutants also (i) gained greater replication ability in cultured cells and in chicken embryos as well as (ii) increased acid and thermal stability but (iii) lost preferences for binding to human-type receptor while maintaining binding for the avian-like receptor. Therefore, they potentially pose reduced pandemic risk. However, the emergent virus variants containing the indicated mutations remain a significant risk to poultry due to antigenic drift and improved fitness for poultry.

Project description:Highly pathogenic avian influenza H5 viruses have pandemic potential, cause significant economic losses and are of veterinary and public health concerns. This study aimed to investigate the distribution and diversity of hemagglutinin (HA) subtypes of avian influenza virus (AIV) in poultry and wild birds in Bangladesh. We conducted an avian influenza sero-surveillance in wild and domestic birds in wetlands of Chattogram and Sylhet in the winter seasons 2012-2014. We tested serum samples using a competitive enzyme-linked immunosorbent assay (c-ELISA), and randomly selected positive serum samples (170 of 942) were tested using hemagglutination inhibition (HI) to detect antibodies against the 16 different HA sero-subtypes. All AIV sero-subtypes except H7, H11, H14 and H15 were identified in the present study, with H5 and H9 dominating over other subtypes, regardless of the bird species. The diversity of HA sero-subtypes within groups ranged from 3 (in household chickens) to 10 (in migratory birds). The prevalence of the H5 sero-subtype was 76.3% (29/38) in nomadic ducks, 71.4% (5/7) in household chicken, 66.7% (24/36) in resident wild birds, 65.9% (27/41) in migratory birds and 61.7% (29/47) in household ducks. Moreover, the H9 sero-subtype was common in migratory birds (56%; 23/41), followed by 38.3% (18/47) in household ducks, 36.8% (14/38) in nomadic ducks, 30.6% (11/66) in resident wild birds and 28.5% (2/7) in household chickens. H1, H4 and H6 sero-subtypes were the most common sero-subtypes (80%; 8/10, 70%; 7/10 and 70%; 7/10, respectively) in migratory birds in 2012, H9 in resident wild birds (83.3%; 5/6) and H2 in nomadic ducks (73.9%; 17/23) in 2013, and the H5 sero-subtype in all types of birds (50% to 100%) in 2014. The present study demonstrates that a high diversity of HA subtypes circulated in diverse bird species in Bangladesh, and this broad range of AIV hosts may increase the probability of AIVs' reassortment and may enhance the emergence of novel AIV strains. A continued surveillance for AIV at targeted domestic-wild bird interfaces is recommended to understand the ecology and evolution of AIVs.

Dataset Information

Receptor binding profiles of avian influenza virus hemagglutinin subtypes on human cells as a predictor of pandemic potential.

Publications

Receptor binding profiles of avian influenza virus hemagglutinin subtypes on human cells as a predictor of pandemic potential.

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