Influenza binds phosphorylated glycans from human lung

Byrd-Leotis, Lauren; Jia, Nan; Dutta, Sucharita; Trost, Jessica F.; Gao, Chao; Cummings, Sandra F.; Braulke, Thomas; Müller‐Loennies, Sven; Heimburg-Molinaro, Jamie; Steinhauer, David A.; Cummings, Richard D.

doi:10.1126/sciadv.aav2554

Cited by 69 publications

(85 citation statements)

References 43 publications

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“…Indeed, studies utilising glycan arrays clearly demonstrate that in addition to SIA‐linkage, other glycan properties such as branch patterns, chain length and modifications (e.g., fucosylation and sulphation) also modulate IAV attachment (reviewed in Viswanathan et al, ). Recent examination of the N ‐glycome of the human lung confirmed the importance of sialylated glycans for the binding of mammalian and avian IAV strains, but this study also demonstrated binding to phosphorylated, nonsialylated glycans, possibly through interactions with the viral HA and/or NA (Byrd‐Leotis et al, ).…”

Section: Susceptibility Of Host Cells To Iav Infection: Host and Virasupporting

confidence: 57%

Influenza A virus interactions with macrophages: Lessons from epithelial cells

Meischel

Villalón-Letelier

Saunders

et al. 2020

Cellular Microbiology

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Influenza viruses are an important cause of respiratory infection worldwide. In humans, infection with seasonal influenza A virus (IAV) is generally restricted to the respiratory tract where productive infection of airway epithelial cells promotes viral amplification, dissemination, and disease. Alveolar macrophages (MΦ) are also among the first cells to detect and respond to IAV, where they play a pivotal role in mounting effective innate immune responses. In contrast to epithelial cells, IAV infection of MΦ is a “dead end” for most seasonal strains, where replication is abortive and newly synthesised virions are not released. Although the key replicative stages leading to productive IAV infection in epithelial cells are defined, there is limited knowledge about the abortive IAV life cycle in MΦ. In this review, we will explore host factors and viral elements that support the early stages (entry) through to the late stages (viral egress) of IAV replication in epithelial cells. Similarities, differences, and unknowns for each key stage of the IAV replicative cycle in MΦ will then be highlighted. Herein, we provide mechanistic insights into MΦ‐specific control of seasonal IAV replication through abortive infection, which may in turn, contribute to effective host defence.

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Section: Susceptibility Of Host Cells To Iav Infection: Host and Virasupporting

confidence: 57%

Influenza A virus interactions with macrophages: Lessons from epithelial cells

Meischel

Villalón-Letelier

Saunders

et al. 2020

Cellular Microbiology

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“…Moreover, due to its high fluorescence sensitivity and conjugation yield, AEAB is ideal for development of natural glycan microarrays or shotgun glycomics, whereby all types of glycans could be isolated from natural sources and be fluorescently-tagged, purified by multi-dimensional chromatography, quantified and eventually printed on glass slides to create natural glycan microarrays. With this approach, we developed a variety of sequence-defined and shotgun glycan microarrays, including a human milk glycan array, a microbial glycan microarray (MGM), sequence-defined and shotgun Schistosome glycan arrays, a pig lung N-glycan array and more recently, a sequence-defined NCFG array, a lectin QA/QC array and a human lung shotgun N-glycan array (Byrd-Leotis et al, 2019b).…”

Section: Development Of Fluorescent Bi-functional Linkermentioning

confidence: 99%

“…This led to the broad screening of various strains of influenza viruses, including these H3N2 strains that have progressively undergone "antigenic drift" in their head domains (Byrd-Leotis et al, 2019a) Surprisingly, the H3N2 drift strains almost completely lost their capacity in binding of canonical sialylated N-glycans on the sequence-defined N-glycan array (Byrd-Leotis et al, 2019a). Moreover, the discoveries with the pig lung glycan array opened the door to later studies with actual human lung tissue to search for endogenous receptors for influenza viruses (Byrd-Leotis et al, 2019b). Interestingly, it was discovered that many of the influenza viruses tested not only bound to sialylated structures, but also to phosphorylated glycans present in human lung tissue (Byrd-Leotis et al, 2019b).…”

Section: Discovery Of Natural Glycan Ligands Involved In Infection Anmentioning

confidence: 99%

“…Moreover, the discoveries with the pig lung glycan array opened the door to later studies with actual human lung tissue to search for endogenous receptors for influenza viruses (Byrd-Leotis et al, 2019b). Interestingly, it was discovered that many of the influenza viruses tested not only bound to sialylated structures, but also to phosphorylated glycans present in human lung tissue (Byrd-Leotis et al, 2019b). This novel finding will lead to brand new lines of study into viral pathogenesis and treatment options.…”

Section: Discovery Of Natural Glycan Ligands Involved In Infection Anmentioning

confidence: 99%

“…Immune checkpoint molecules PD-1 (Okada et al, 2017) and PD-L1 Lee et al, 2019) are both heavily glycosylated, and the glycans are required for their normal interactions and subsequent suppression of T cell activities. In addition, human glycans are receptors of surface proteins of pathogens, such as bacteria, fungi and viruses that are involved in virtually all types of infectious disease processes (Li et al, 2017;Byrd-Leotis et al, 2019b).…”

Section: Introductionmentioning

confidence: 99%

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Glycan Microarrays as Chemical Tools for Identifying Glycan Recognition by Immune Proteins

et al. 2019

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Glycans and glycan binding proteins (GBPs or lectins) are essential components in almost every aspect of immunology. Investigations of the interactions between glycans and GBPs have greatly advanced our understanding of the molecular basis of these fundamental immunological processes. In order to better study the glycan-GBP interactions, microscope glass slide-based glycan microarrays were conceived and proved to be an incredibly useful and successful tool. A variety of methods have been developed to better present the glycans so that they mimic natural presentations. Breakthroughs in chemical biology approaches have also made available glycans with sophisticated structures that were considered practically impossible just a few decade ago. Glycan microarrays provide a wealth of valuable information in immunological studies. They allow for discovery of detailed glycan binding preferences or novel binding epitopes of known endogenous immune receptors, which can potentially lead to the discovery of natural ligands that carry the glycans. Glycan microarrays also serve as a platform to discover new GBPs that are vital to the process of infection and invasion by microorganisms. This review summarizes the construction strategies and the immunological applications of glycan microarrays, particularly focused on those with the most comprehensive sets of glycan structures. We also review new methods and technologies that have evolved. We believe that glycan microarrays will continue to benefit the growing research community with various interests in the field of immunology.

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LectinOracle: A Generalizable Deep Learning Model for Lectin–Glycan Binding Prediction

Lundstrøm

Korhonen

Lisacek³

et al. 2021

Advanced Science

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Ranging from bacterial cell adhesion over viral cell entry to human innate immunity, glycan-binding proteins or lectins are abound in nature. Widely used as staining and characterization reagents in cell biology and crucial for understanding the interactions in biological systems, lectins are a focal point of study in glycobiology. Yet the sheer breadth and depth of specificity for diverse oligosaccharide motifs has made studying lectins a largely piecemeal approach, with few options to generalize. Here, LectinOracle, a model combining transformer-based representations for proteins and graph convolutional neural networks for glycans to predict their interaction, is presented. Using a curated data set of 564,647 unique protein-glycan interactions, it is shown that LectinOracle predictions agree with literature-annotated specificities for a wide range of lectins. Using a range of specialized glycan arrays, it is shown that LectinOracle predictions generalize to new glycans and lectins, with qualitative and quantitative agreement with experimental data. It is further demonstrated that LectinOracle can be used to improve lectin classification, accelerate lectin directed evolution, predict epidemiological outcomes in the context of influenza virus, and analyze whole lectomes in host-microbe interactions. It is envisioned that the herein presented platform will advance both the study of lectins and their role in (glyco)biology.

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Influenza binds phosphorylated glycans from human lung

Abstract: A novel array of human lung glycans reveals influenza A virus binding to phosphorylated as well as sialylated N-glycans.

Cited by 69 publications

References 43 publications

Influenza A virus interactions with macrophages: Lessons from epithelial cells

Influenza A virus interactions with macrophages: Lessons from epithelial cells

Glycan Microarrays as Chemical Tools for Identifying Glycan Recognition by Immune Proteins

LectinOracle: A Generalizable Deep Learning Model for Lectin–Glycan Binding Prediction

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