Contemporary human H3N2 influenza A viruses require a low threshold of suitable glycan receptors for efficient infection

Spruit, Cindy M.; Sweet, Igor R; Maliepaard, Joshua C.L.; Bestebroer, Theo M.; Lexmond, Pascal; Qiu, Boning; Damen, Mirjam J; Fouchier, Ron A. M.; Reiding, Karli R.; Snijder, Joost; Herfst, Sander; Boons, Geert‐Jan; Vries, Robert P. de

doi:10.1093/glycob/cwad060

Cited by 10 publications

(14 citation statements)

References 74 publications

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“…We hypothesize that this binding pattern relates to a balancing act between antigenic divergence and glycan binding properties to the more abundant of 2,6-sialylated di-LacNAc structures. 19 Our data shows that this is not only a property of A(H3N2) but also for A(H1N1)pdm09 viruses.…”

Section: Introductionmentioning

confidence: 54%

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Asymmetrical Bi-antennary Glycans Prepared by a Stop-and-Go Strategy Reveal Receptor Binding Evolution of Human Influenza A Viruses

Ma,

Liu,

Eggink

et al. 2023

Preprint

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Glycan binding properties of respiratory viruses have been difficult to probe due to a lack of biological relevant glycans for binding studies. Here, a stop-and-go chemoenzymatic methodology is presented that gave access to a panel of 32 asymmetrical bi-antennaryN-glycans having various numbers ofN-acetyl lactosamine (LacNAc) repeating units capped by α2,3- or α2,6-sialosides resembling structures found in airway tissues. It exploits that the branching enzymes MGAT1 and MGAT2 can utilize unnatural UDP-2-deoxy-2-trifluoro-N-acetamido-glucose (UDP-GlcNTFA) as donor. The TFA moiety of the resulting glycans can be hydrolyzed to give GlcNH2at one of the antennae that temporarily blocks extension by glycosyl transferases. TheN-glycans were printed as a microarray that was probed for receptor binding specificities of evolutionary distinct human A(H3N2) and A(H1N1)pdm09 viruses. It was found that not only the sialoside type but also the length of the LacNAc chain and presentation at the α1,3-antenna ofN-glycans is critical for binding. Early A(H3N2) viruses bound to 2,6-sialosides at a single LacNAc moiety at the α1,3-antenna whereas later viruses required the sialoside to be presented at a tri-LacNAc moiety. Surprisingly, most of the A(H3N2) viruses that appeared after 2021 regained binding capacity to sialosides presented at a di-LacNAc moiety. As a result, these viruses agglutinate erythrocytes again, commonly employed for antigenic characterization of influenza viruses. Human A(H1N1)pdm09 viruses have similar receptor binding properties as recent A(H3N2) viruses. The data indicates that an asymmetricN-glycan having 2,6-sialoside at a di-LacNAc moiety is a commonly employed receptor by human influenza A viruses.

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Section: Introductionmentioning

confidence: 54%

“…It is likely that the di-LacNAc moiety allows for additional interactions with HA for sufficient high affinity of binding to compensate for reduced binding of sialic acid due to mutational changes caused by antigenic pressure. 19…”

Section: Discussionmentioning

confidence: 99%

Asymmetrical Bi-antennary Glycans Prepared by a Stop-and-Go Strategy Reveal Receptor Binding Evolution of Human Influenza A Viruses

Ma,

Liu,

Eggink

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, recently this trend reversed and most strains that appeared after 2021 also exhibit some affinity for 2,6-sialosides presented on a di-LacNAc moiety. We hypothesize that this binding pattern relates to a balancing act between antigenic divergence and glycan binding properties to the more abundant of 2,6-sialylated di-LacNAc structures . Our data show that this is a property not only of A(H3N2) but also of A(H1N1)pdm09 viruses.…”

Section: Introductionmentioning

confidence: 65%

“…Thus, a 2,6-sialoside at a di-LacNAc moiety presented at the α1,3-antenna appears to be a commonly employed receptor for human influenza A viruses. It is likely that the di-LacNAc moiety allows for additional interactions with HA for sufficient high affinity of binding to compensate for reduced binding of sialic acid due to mutational changes caused by antigenic pressure …”

Section: Discussionmentioning

confidence: 99%

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Asymmetrical Biantennary Glycans Prepared by a Stop-and-Go Strategy Reveal Receptor Binding Evolution of Human Influenza A Viruses

Ma,

Liu,

Eggink

et al. 2024

JACS Au

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Glycan binding properties of respiratory viruses have been difficult to probe due to a lack of biologically relevant glycans for binding studies. Here, a stop-and-go chemoenzymatic methodology is presented that gave access to a panel of 32 asymmetrical biantennary N-glycans having various numbers of N-acetyl lactosamine (LacNAc) repeating units capped by α2,3or α2,6-sialosides resembling structures found in airway tissues. It exploits that the branching enzymes MGAT1 and MGAT2 can utilize unnatural UDP-2-deoxy-2-trifluoro-N-acetamido-glucose (UDP-GlcNTFA) as donor. The TFA moiety of the resulting glycans can be hydrolyzed to give GlcNH 2 at one of the antennae, which temporarily blocks extension by glycosyl transferases. The N-glycans were printed as a microarray that was probed for receptor binding specificities of the evolutionary distinct human A(H3N2) and A(H1N1)pdm09 viruses. It was found that not only the sialoside type but also the length of the LacNAc chain and presentation at the α1,3-antenna of N-glycans are critical for binding. Early A(H3N2) viruses bound to 2,6-sialosides at a single LacNAc moiety at the α1,3-antenna whereas later viruses required the sialoside to be presented at a tri-LacNAc moiety. Surprisingly, most of the A(H3N2) viruses that appeared after 2021 regained binding capacity to sialosides presented at a di-LacNAc moiety. As a result, these viruses again agglutinate erythrocytes, commonly employed for antigenic characterization of influenza viruses. Human A(H1N1)pdm09 viruses have similar receptor binding properties as recent A(H3N2) viruses. The data indicate that an asymmetric N-glycan having 2,6-sialoside at a di-LacNAc moiety is a commonly employed receptor by human influenza A viruses.

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Viral envelope proteins fused to multiple distinct fluorescent reporters to probe receptor binding

Tomris,

van der Woude,

de Paiva Froes Rocha

et al. 2024

Protein Science

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Enveloped viruses carry one or multiple proteins with receptor‐binding functionalities. Functional receptors can be glycans, proteinaceous, or both; therefore, recombinant protein approaches are instrumental in attaining new insights regarding viral envelope protein receptor‐binding properties. Visualizing and measuring receptor binding typically entails antibody detection or direct labeling, whereas direct fluorescent fusions are attractive tools in molecular biology. Here, we report a suite of distinct fluorescent fusions, both N‐ and C‐terminal, for influenza A virus hemagglutinins and SARS‐CoV‐2 spike RBD. The proteins contained three or six fluorescent protein barrels and were applied directly to cells to assess receptor binding properties.

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Contemporary human H3N2 influenza A viruses require a low threshold of suitable glycan receptors for efficient infection

Cited by 10 publications

References 74 publications

Asymmetrical Bi-antennary Glycans Prepared by a Stop-and-Go Strategy Reveal Receptor Binding Evolution of Human Influenza A Viruses

Asymmetrical Bi-antennary Glycans Prepared by a Stop-and-Go Strategy Reveal Receptor Binding Evolution of Human Influenza A Viruses

Asymmetrical Biantennary Glycans Prepared by a Stop-and-Go Strategy Reveal Receptor Binding Evolution of Human Influenza A Viruses

Viral envelope proteins fused to multiple distinct fluorescent reporters to probe receptor binding

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