A gel-capture assay for characterizing the sialyl-glycan selectivity of influenza viruses

Velkov, Tony; Thompson, Phillip E.; El‐Kabbani, Ossama; Lindh, Frank; Stambas, John; Rockman, Steve

doi:10.4149/av_2011_02_131

Cited by 2 publications

(2 citation statements)

References 31 publications

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“…The tertiary receptor binding site then interacts with the sialic acid linkages on the surface of respiratory cells [ 18 ]. Human influenza viruses, including both lineages of IBV, bind preferentially to α2,6 linked sialic acid residues [ 19 , 20 , 21 , 22 , 23 , 24 ]. Avian IAV strains preferentially bind α2,3 linked-sialic acids [ 12 , 25 ].…”

Section: Hemagglutinin-specific Adaptationsmentioning

confidence: 99%

Existing Evidence for Influenza B Virus Adaptations to Drive Replication in Humans as the Primary Host

Pekarek,

Weaver

2023

Viruses

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Influenza B virus (IBV) is one of the two major types of influenza viruses that circulate each year. Unlike influenza A viruses, IBV does not harbor pandemic potential due to its lack of historical circulation in non-human hosts. Many studies and reviews have highlighted important factors for host determination of influenza A viruses. However, much less is known about the factors driving IBV replication in humans. We hypothesize that similar factors influence the host restriction of IBV. Here, we compile and review the current understanding of host factors crucial for the various stages of the IBV viral replication cycle. While we discovered the research in this area of IBV is limited, we review known host factors that may indicate possible host restriction of IBV to humans. These factors include the IBV hemagglutinin (HA) protein, host nuclear factors, and viral immune evasion proteins. Our review frames the current understanding of IBV adaptations to replication in humans. However, this review is limited by the amount of research previously completed on IBV host determinants and would benefit from additional future research in this area.

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Section: Hemagglutinin-specific Adaptationsmentioning

confidence: 99%

Existing Evidence for Influenza B Virus Adaptations to Drive Replication in Humans as the Primary Host

Pekarek,

Weaver

2023

Viruses

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“…We, and others identified mutation sites in the HA molecule that significantly facilitated viral rescue and amplification in eggs namely, K123N, D225G and Q226R [32,33,34]. To understand how these important mutations impact on the receptor binding preference of these key H1N1 2009 vaccine strains, we have now examined the glycan selectivity of each HA variant using a solid-phase ELISA glycan binding assay with both whole viruses and purified recombinant HAs [35,36]. Furthermore, homology-based structural models of the various HA molecules complexed to receptor analogs were constructed to assess amino acid differences within the binding pocket can change HA avidity for human and avian glycans.…”

Section: Introductionmentioning

confidence: 99%

Molecular Characterisation of the Haemagglutinin Glycan-Binding Specificity of Egg-Adapted Vaccine Strains of the Pandemic 2009 H1N1 Swine Influenza A Virus

et al. 2015

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Abstract:The haemagglutinin (HA) glycan binding selectivity of H1N1 influenza viruses is an important determinant for the host range of the virus and egg-adaption during vaccine production. This study integrates glycan binding data with structure-recognition models to examine the impact of the K123N, D225G and Q226R mutations (as seen in the HA of vaccine strains of the pandemic 2009 H1N1 swine influenza A virus). The glycan-binding selectivity of three A/California/07/09 vaccine production strains, and purified recombinant A/California/07/09 HAs harboring these mutations was examined via a solid-phase ELISA assay. Wild-type A/California/07/09 recombinant HA bound specifically to α2,6-linked sialyl-glycans, with no affinity for the α2,3-linked sialyl-glycans in the array. In contrast, the OPEN ACCESSMolecules 2015, 20 10416 vaccine virus strains and recombinant HA harboring the Q226R HA mutation displayed a comparable pattern of highly specific binding to α2,3-linked sialyl-glycans, with a negligible affinity for α2,6-linked sialyl-glycans. The D225G A/California/07/09 recombinant HA displayed an enhanced binding affinity for both α2,6-and α2,3-linked sialyl-glycans in the array. Notably its α2,6-glycan affinity was generally higher compared to its α2,3-glycan affinity, which may explain why the double mutant was not naturally selected during egg-adaption of the virus. The K123N mutation which introduces a glycosylation site proximal to the receptor binding site, did not impact the α2,3/α2,6 glycan selectivity, however, it lowered the overall glycan binding affinity of the HA; suggesting glycosylation may interfere with receptor binding. Docking models and 'per residues' scoring were employed to provide a structure-recognition rational for the experimental glycan binding data. Collectively, the glycan binding data inform future vaccine design strategies to introduce the D225G or Q226R amino acid substitutions into recombinant H1N1 viruses.

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A gel-capture assay for characterizing the sialyl-glycan selectivity of influenza viruses

Cited by 2 publications

References 31 publications

Existing Evidence for Influenza B Virus Adaptations to Drive Replication in Humans as the Primary Host

Existing Evidence for Influenza B Virus Adaptations to Drive Replication in Humans as the Primary Host

Molecular Characterisation of the Haemagglutinin Glycan-Binding Specificity of Egg-Adapted Vaccine Strains of the Pandemic 2009 H1N1 Swine Influenza A Virus

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